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    Soy isoflavones exert modest hormonal effects in premenopausal women. Duncan A M,Merz B E,Xu X,Nagel T C,Phipps W R,Kurzer M S The Journal of clinical endocrinology and metabolism Soy isoflavones are hypothesized to be responsible for changes in hormone action associated with reduced breast cancer risk. To test this hypothesis, we studied the effects of isoflavone consumption in 14 premenopausal women. Isoflavones were consumed in soy protein powders and provided relative to body weight (control diet, 10 +/- 1.1; low isoflavone diet, 64 +/- 9.2; high isoflavone diet, 128 +/- 16 mg/day) for three menstrual cycles plus 9 days in a randomized cross-over design. During the last 6 weeks of each diet period, plasma was collected every other day for analysis of estrogens, progesterone, LH, and FSH. Diet effects were assessed during each of four distinctly defined menstrual cycle phases. Plasma from the early follicular phase was analyzed for androgens, cortisol, thyroid hormones, insulin, PRL, and sex hormone-binding globulin. The low isoflavone diet decreased LH (P = 0.009) and FSH (P = 0.04) levels during the periovulatory phase. The high isoflavone diet decreased free T3 (P = 0.02) and dehydroepiandrosterone sulfate (P = 0.02) levels during the early follicular phase and estrone levels during the midfollicular phase (P = 0.02). No other significant changes were observed in hormone concentrations or in the length of the menstrual cycle, follicular phase, or luteal phase. Endometrial biopsies performed in the luteal phase of cycle 3 of each diet period revealed no effect of isoflavone consumption on histological dating. These data suggest that effects on plasma hormones and the menstrual cycle are not likely to be the primary mechanisms by which isoflavones may prevent cancer in premenopausal women. 10.1210/jcem.84.1.5387
    Effects of an isoflavone-free soy diet on ovarian hormones in premenopausal women. Lu L J,Anderson K E,Grady J J,Nagamani M The Journal of clinical endocrinology and metabolism Soy intakes have been associated with reduced rates of breast cancer in some Asian populations. The isoflavones daidzein and genistein and other components of soybeans may modulate endocrine function and lead to beneficial health effects. This study determined the effects of a soy diet containing minimum amounts of isoflavones on circulating levels of ovarian hormones and gonadotropins. Nine healthy, regularly cycling women consumed a constant soya-containing diet on a metabolic unit starting on day 2 of a menstrual cycle until day 2 of the next cycle. The soy diet was calculated to maintain constant body weight and included a 36-oz portion of soymilk that provided 334 kilocalories and less than 5 mg/day of total isoflavones. The energy distribution of the soy diet was 35.9% fat, 14.0% protein, and 49.8% carbohydrate whereas the home diets averaged 39% fat, 16.6% protein, and 42.5% carbohydrate. For the group, the soya diet provided more carbohydrate (P = 0.002) and less protein (P = 0.005) than the home diets. Daily consumption of the soya diet reduced daily circulating levels of 17beta-estradiol over the entire menstrual cycle by 20% (P < 0.01, paired t test, two-tailed) and progesterone by 33% (P < 0.0001) compared with levels during the home diet period, but had no effect on LH, FSH, or sex hormone-binding globulin. The decreases in follicular phase 17beta-estradiol during the soy diet can be accounted for by changes in energy intakes, nutrient density, and fiber intake, whereas changes in luteal phase 17beta-estradiol were most strongly associated with differences in fiber intake. Changes in progesterone levels were most strongly associated with changes in protein intake and much less with other nutrients. Isoflavones were not detectable in plasma and urine during either the soy or home diet periods. These results suggest that at least under the conditions of this study, a soy diet with low levels of isoflavones and low energy intake from protein can reduce circulating ovarian steroids without altering gonadotropins. Our results are consistent with previous studies showing decreased ovarian hormone levels and decreased risk of breast cancer in populations consuming soya diets and an inverse relationship between animal protein intake and breast cancer risk and, therefore, may have implications for breast cancer prevention. 10.1210/jcem.86.7.7684
    Effect of adding dietary methionine to a low soy protein diet on the brain protein synthesis rate in ovariectomized female rats. Lyou Sunok,Tujioka Kazuyo,Hirano Emi,Mawatari Yuka,Hayase Kazutoshi,Okuyama Satoshi,Yokogoshi Hidehiko Nutritional neuroscience A deficiency of sex hormones affects brain function in mammals, including the decrease of protein synthesis. Recently, we have shown that the protein synthesis in the brain depended on the quality of dietary protein in ovariectomized female rats. The methionine is the first limiting amino acid for the recommended dietary allowance of amino acids in soy protein. The purpose of this study was to determine whether the addition of dietary methionine affected the rate of brain protein synthesis in ovariectomized female rats fed on the soy protein diet. Experiments were conducted on two groups of ovariectomized female rats (24 week) given the diets containing 5% soy protein or 5% soy protein + 0.2% methionine for 10 d. The fractional rates of protein synthesis in cerebral cortex and cerebellum significantly increased with an addition of dietary methionine. In the brain, the RNA activity [g protein synthesized/((g RNA) x d)] was significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg of RNA/g of protein) was not related to the fractional rate of protein synthesis in any organ. The results suggest that the addition of limiting amino acid for the low soy protein elevates the rate of protein synthesis in the brain of ovariectomized female rats, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis. 10.1080/10284150412331279818
    Hormonal response to diets high in soy or animal protein without and with isoflavones in moderately hypercholesterolemic subjects. Goldin Barry R,Brauner Edgard,Adlercreutz Herman,Ausman Lynne M,Lichtenstein Alice H Nutrition and cancer Consumption of soy protein has been associated with altered risk of developing endocrine-regulated cancers. This study was designed to assess the independent effect of soy relative to animal protein and soy-derived isoflavones on circulating estrogen and androgen concentrations in postmenopausal women and older men. Forty-two subjects (> 50 yr) with low-density lipoprotein cholesterol levels of > or = 3.36 mmol/l were fed each of 4 diets in randomized order for 6 wk/phase. All food and drink were provided. Diets contained 25 g soy or common sources of animal protein/4.2 MJ containing trace or 50 mg isoflavones/4.2 MJ. At the end of each diet phase, concentrations of estrone sulfate, estrone, estradiol, testosterone, androstendione, dihydrotestosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were measured. In postmenopausal women, concentrations of estrone were higher and its precursor, dehydroepiandrosterone, lower after consuming the soy compared with animal protein diets (P = 0.0396 and 0.0374, respectively). There was no significant effect of isoflavones on any of the hormones measured. In older men, dehydroepiandrosterone sulfate concentrations were lower after consuming the isoflavone (P = 0.0106) and higher after soy, compared with the animal protein diets (P = 0.0118). These data suggest that relatively large amounts of soy protein or soy-derived isoflavones had modest and limited sex-specific effects on circulating hormone levels. 10.1207/s15327914nc5101_1
    Age-related renal disease in female Dahl salt-sensitive rats is attenuated with 17 beta-estradiol supplementation by modulating nitric oxide synthase expression. Maric Christine,Xu Qin,Sandberg Kathryn,Hinojosa-Laborde Carmen Gender medicine. official journal of the Partnership for Gender-Specific Medicine at Columbia University BACKGROUND:The incidence of chronic renal disease in women increases with aging, especially after menopause, suggesting that loss of sex hormones may contribute to the development and progression of renal disease. However, the mechanisms by which sex hormones, particularly estrogens, contribute to the disease process are unclear. OBJECTIVE:The present study examined the effects of ovariectomy (OVX) with or without 17 beta-estradiol (E2) supplementation (OVX+E2) on the expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase in the kidney. METHODS:The study was performed in young (4 months [4M]) and aged (12 months [12M]) female Dahl salt-sensitive rats fed a low-sodium (0.1% NaCl) diet. At 3 months of age, the animals were either subjected to sham surgery, OVX, or OVX with implantation of an E2 silastic pellet. The treatments were administered for either 1 or 9 months, rendering the animals 4 months of age or 12 months of age at the time of sacrifice, respectively. Renal expression of NOS isoforms was measured by Western blotting and immunohistochemistry. RESULTS:OVX in the aged rats was associated with 35% and 25% decreases in medullary iNOS (mean [SEM] relative optical density [ROD]: 4M OVX, 1.81 [0.14] vs 12M OVX, 1.17 [0.16]; P < 0.05) and eNOS (mean ROD: 4M OVX, 1.91 [0.09] vs 12M OVX, 1.43 [0.15]; P < 0.05) protein expression, respectively, and a 25-fold increase in the abundance of CD68-positive cells, indicating macrophage infiltration (mean cells/mm2: 4M OVX, 1.18 [0.09] vs 12M OVX, 30.0 [0.74]; P < 0.001). E2 supplementation either partially or completely attenuated these changes in iNOS (mean ROD: 4M OVX+E2, 2.26 [0.08] vs 12M OVX+E2, 1.70 [0.09]; P < 0.05), eNOS (mean ROD: 4M OVX+E2, 2.03 [0.07] vs 12M OVX+E2, 1.77 [0.11]; P = NS) and CD68 (mean cells/mm2: 4M OVX+E2, 1.46 [0.07] vs 12M OVX+E2, 6.87 [1.6]; P < 0.01) associated with OVX in the aging kidney. CONCLUSIONS:These data suggest that ovarian E2 loss with aging may contribute to the development of age-related renal disease through downregulation of iNOS and eNOS protein abundance and increased renal inflammation in this animal model. Furthermore, E2 supplementation may be protective in the aging kidney by attenuating these changes. 10.1016/j.genm.2008.05.002
    Effects of dietary protein content on IGF-I, testosterone, and body composition during 8 days of severe energy deficit and arduous physical activity. Alemany Joseph A,Nindl Bradley C,Kellogg Mark D,Tharion William J,Young Andrew J,Montain Scott J Journal of applied physiology (Bethesda, Md. : 1985) Energy restriction coupled with high energy expenditure from arduous work is associated with an altered insulin-like growth factor-I (IGF-I) system and androgens that are coincident with losses of fat-free mass. The aim of this study was to determine the effects of two levels of dietary protein content and its effects on IGF-I, androgens, and losses of fat-free mass accompanying energy deficit. We hypothesized that higher dietary protein content would attenuate the decline of anabolic hormones and, thus, prevent losses of fat-free mass. Thirty-four men [24 (SD 0.3) yr, 180.1 (SD 1.1) cm, and 83.0 (SD 1.4) kg] participated in an 8-day military exercise characterized by high energy expenditure (16.5 MJ/day), low energy intake (6.5 MJ/day), and sleep deprivation (4 h/24 h) and were randomly divided into two dietary groups: 0.9 and 0.5 g/kg dietary protein intake. IGF-I system analytes, androgens, and body composition were assessed before and on days 4 and 8 of the intervention. Total, free, and nonternary IGF-I and testosterone declined 50%, 64%, 55%, and 45%, respectively, with similar reductions in both groups. There was, however, a diet x time interaction on day 8 for total IGF-I and sex hormone-binding globulin. Decreases in body mass (3.2 kg), fat-free mass (1.2 kg), fat mass (2.0 kg), and percent body fat (1.5%) were similar in both groups (P = 0.01). Dietary protein content of 0.5 and 0.9 g/kg minimally attenuated the decline of IGF-I, the androgenic system, and fat-free mass during 8 days of negative energy balance associated with high energy expenditure and low energy intake. 10.1152/japplphysiol.00005.2008
    Effects of Dietary Approach to Stop Hypertension diet on androgens, antioxidant status and body composition in overweight and obese women with polycystic ovary syndrome: a randomised controlled trial. Azadi-Yazdi M,Karimi-Zarchi M,Salehi-Abargouei A,Fallahzadeh H,Nadjarzadeh A Journal of human nutrition and dietetics : the official journal of the British Dietetic Association BACKGROUND:Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive age women. The present study aimed to determine the effects of Dietary Approaches to Stop Hypertension (DASH) diet on reproductive hormones, plasma total antioxidant status and anthropometric indices in overweight and obese PCOS women. METHODS:In this randomised controlled clinical trial, 60 women with PCOS were randomly assigned to one of two diets with energy restriction: the DASH diet and a control diet. The DASH and control diets consisted of 50-55% carbohydrate, 15-20% protein and 25-30% total fat. The DASH diet was designed to be rich in vegetables, fruits, whole grains and low-fat dairy products, as well as low in saturated fats, cholesterol, refined grains and sweets. In the present study, the anthropometric indices, body composition, total testosterone, androstenedione, sex hormone binding globulin (SHBG), free androgen index and 2,2'-diphenyl-1-picryylhydrazyl (DPPH) scavenging activity were measured before and after 3 months. RESULTS:The consumption of DASH diet compared to the control diet was associated with a significant reduction in weight [-5.78 (1.91) kg versus -4.34 (2.87) kg, P = 0.032], body mass index (BMI) [-2.29 (0.15) kg m versus -1.69 (0.20) kg m , P = 0.02], fat mass [-3.23(1.66) kg versus -2.13 (1.26) kg, P = 0.008] and serum androstenedione [-1.75 (1.39) ng mL versus -1.02 (0.72) ng mL , P-value = 0.019]. Increased concentrations of SHBG [28.80 (21.71) versus 11.66(18.82) nmol L , P = 0.003) and DPPH scavenging activity [30.23% (19.09) versus 12.97% (25.12) were also found in the DASH group. CONCLUSIONS:The DASH diet could improve weight loss, BMI and fat mass. Furthermore, it could result in a significant reduction in serum androstenedione and a significant increase in antioxidant status and SHBG. 10.1111/jhn.12433
    Perinatal free-choice of a high-calorie low-protein diet affects leptin signaling through IRS1 and AMPK dephosphorylation in the hypothalami of female rat offspring in adulthood. Rivera Patricia,Ramírez-López María T,Vargas Antonio,Decara Juan,Vázquez Mariam,Arco Rocío,Gómez de Heras Raquel,Argente Jesús,Rodríguez de Fonseca Fernando,Chowen Julie A,Suárez Juan Acta physiologica (Oxford, England) AIM:We aimed to investigate whether a dysregulated maternal diet during gestation and lactation induces long-lasting changes in the hypothalamic control of feeding behavior in the offspring and whether this effect is sex specific. METHODS:The study included an analysis of appetite-regulating metabolic hormones and hypothalamic signaling in male and female offspring in adulthood after exposure to a free-choice high-calorie palatable low-protein (P) diet or standard chow (C) during (pre)gestation/lactation (maternal) and/or postweaning (offspring). RESULTS:Maternal exposure to the P diet resulted in decreased protein intake and body weight gain in dams and decreased body weight gain in offspring during lactation. The maternal P diet (PC) specifically increased feed efficacy and decreased body weight and cholesterol levels in the female offspring in adulthood, but no changes in adiposity or leptin levels were found. In contrast, P diet exposure after weaning (CP and PP) increased caloric intake, adiposity and circulating levels of leptin in the male and female offspring in adulthood. The hypothalami of the female offspring exposed to the maternal P diet (PC and PP) expressed high levels of the phospho-leptin receptor and low levels of SOCS3, phospho-IRS1 and phospho-AMPK, regardless of the postweaning diet. The hypothalami of the female rats in the PC group also showed increased levels of STAT3 and the orexigenic neuropeptide Agrp. CONCLUSIONS:Maternal exposure to a free-choice high-calorie low-protein diet induces a long-term feed efficacy associated with changes in leptin signaling through IRS-1 and AMPK dephosphorylation in the hypothalami of female offspring in adulthood. 10.1111/apha.13244
    Effect of malnutrition on the metabolism of sex hormones in man. Fishman J,Bradlow H L Clinical pharmacology and therapeutics 10.1002/cpt1977225part2721
    [Sex hormones binding globulin in lying-in women and their newborn infants with intrauterine malnutrition]. Muzzo S,Zvaighaft A,Cañas P Archivos latinoamericanos de nutricion The purpose of this research was to study the binding capacity of estrogens to the sex hormone-binding globulin (SHBG) in mothers and their intrauterine malnourished newborns. Blood samples were obtained from mothers at delivery, and from babies, of the umbilical cord. SHBG was measured according to the method of Mickelson and Petra. It was found in mothers of malnourished babies that the binding capacity of serum protein to dehydrotestosterone (DHT) was significantly decreased in comparison to the controls (10.63 +/- 1.61 vs 13.25 +/- 2.18 micrograms DHT/dl serum, respectively), whereas it was significantly increased in intrauterine malnourished newborns (1.01 +/- 0.24 vs 0.77 +/- 0.18, respectively). These results suggest that SHBG decrease in mothers of intrauterine malnourished newborns occurs due to a decrease in the production of fetal adrenal hormone precursors and may, therefore, be a compensating mechanism to increase placental flow.
    Male gonadal function in coeliac disease: 2. Sex hormones. Farthing M J,Rees L H,Edwards C R,Dawson A M Gut Hypogonadism, infertility, and sexual dysfunction occur in some men with coeliac disease. We have measured plasma testosterone, dihydrotestosterone, sex-hormone binding globulin, oestradiol, and serum luteinising hormone in 41 men with coeliac disease and have related these findings to jejunal morphology, fertility, semen quality, and sexual function. To determine the specificity of these observations in coeliacs we also studied 19 nutritionally-matched men with Crohn's disease, and men with chronic ill-health due to rheumatoid arthritis and Hodgkin's disease. The most striking endocrine findings in untreated coeliacs were increased plasma testosterone and free testosterone index, reduced dihydrotestosterone (testosterone's potent peripheral metabolite), and raised serum luteinising hormone, a pattern of abnormalities indicative of androgen resistance. As jejunal morphology improved hormone levels appeared to return to normal. This specific combination of abnormalities was not present in any of the disease control groups and, to our knowledge, androgen resistance has not been described previously in any other non-endocrine disorder. Plasma oestradiol concentration was modestly raised in 10% of coeliacs and 11% of patients with Crohn's disease. Unlike plasma androgens and serum luteinising hormone in coeliacs, plasma oestradiol was not clearly related to jejunal morphology. Androgen resistance and associated hypothalamic-pituitary dysfunction appear to be relatively specific to coeliac disease and cannot be explained merely in terms of malnutrition or chronic ill-health. In addition, our findings suggest that this endocrine disturbance may be related to sexual dysfunction in coeliac disease but its relationship to disordered spermatogenesis in this condition has not been clearly established. 10.1136/gut.24.2.127
    Effects of protein energy malnutrition on circulating thyroid hormones. Turkay S,Kus S,Gokalp A,Baskin E,Onal A Indian pediatrics The effect of protein energy malnutrition (PEM) in the children on serum levels of total thyroxine (TT4), total triodothyronine (TT3) and thyrotropin (TSH) were evaluated. There were 107 children aged 2 to 60 months in the malnutrition group and 54 healthy age and sex matched controls. Serum TT4 and TT3 were all reduced in the malnutrition group. This decrease in TT3 was more significant (p < 0.01) in severe malnutrition than in mild PEM. Serum TSH levels in the malnutrition and control groups were similar. These results suggest that the children remained euthyroid and represent an adaptive response to protein energy malnutrition.
    Altered pulsatile gonadotropin signaling in nutritional deficiency in the male. Bergendahl M,Veldhuis J D Trends in endocrinology and metabolism: TEM Reproduction cannot occur without adequate nutrition. Diets that are nutritionally inadequate delay and disrupt the pubertal development of the reproductive processes of immature experimental animals and humans, and impair the function of the hypothalamic-pituitary-gonadal axis in adults. Although there is a general understanding of the linkages between nutrition and reproduction, there is a lack of detailed knowledge of the exact mechanisms that couple these two systems. The major effects of malnutrition on the hypothalamic-pituitary-gonadal axis reported in the literature are, for the most part, manifested as reduced gonadotropin secretion. Malnutrition results in decreased circulating gonadotropin concentrations. These changes in the reproductive system are associated with impaired gonadal function and subsequent secondary sex organ atrophy and lead, ultimately, to poor reproduction. Decreased hypothalamic release of gonadotropin-releasing hormone (GnRH) has been proposed as the most important etiologic factor for the fasting-induced suppression of pituitary-testicular function. In the human, hypogonadism and infertility develop in both sexes during chronic malnutrition. Most studies on the effects of malnutrition on the reproductive hormones have been performed in women, perhaps because malnutrition in women is promptly accompanied by amenorrhea, whereas in men hypogonadism develops gradually and becomes clinically evident only during more severe malnutrition. With the advent of sensitive assays for measuring reproductive hormones and of modern computerized methods for analyzing the pulsatile secretion of these hormones, however, the function of the hypothalamic-pituitary-testicular axis has been scrutinized and it has, indeed, been observed that this system is disturbed even during acute malnutrition. Here, we review the effects of malnutrition on reproductive function, especially on the pulsatile pattern of LH secretion, in humans and in experimental animals. 10.1016/1043-2760(95)00081-r
    [Effect of gonadal hormones on sexual dimorphism in malnutrition substrates]. Orden A B,Pucciarelli H M,Muñe M C,Guimarey L M,Villanueva M E,Rodríguez R R,Pons E R Acta physiologica, pharmacologica et therapeutica latinoamericana : organo de la Asociacion Latinoamericana de Ciencias Fisiologicas y [de] la Asociacion Latinoamericana de Farmacologia The environmental effect on growth and sexual dimorphism is mediated by endocrinological dysfunctions. It was shown that malnutrition acts on the hypotalamus-pituitary-glandular axis. An experiment was made in Wistar rats to determine the effect of some gonadic hormones on the functional components of the skull to which sex dimorphism was alterated by a postnatal undernutrition. The effects of these hormones in restoring sexual cranial dimorphism was tested. Four treatments were applied: control, with food intake ad-libitum; undernutrition (50% of the control food intake); undernutrition plus periodic injections of testosterone and estradiol to males and females, respectively and sham-operated animals, which were injected with oil vehicle only. A radiological longitudinal study was performed between 20 and 80 days of postnatal age. The length width and height of the neural and facial components were measured on each radiograph. Data were processed by ANOVA and Mann-Whitney statistical tests were performed by means of the SYSTAT 7.0 statistical package. Results showed that gonadic hormones restored the sexual cranial dimorphism by stimulating (testosterone) or suppressing (estradiol) the growth of the cranial components.
    Insulin-Like growth factor I: implications in aging. Arvat E,Broglio F,Ghigo E Drugs & aging According to the somatomedin model, growth hormone (GH)-dependent hepatic synthesis is responsible for maintaining circulating insulin-like growth factor (IGF)-I levels. On the other hand, the local autocrine/paracrine IGF-I expression in peripheral tissue is generally GH-independent and reflects the effects of various and tissue-specific trophic hormones. Circulating IGF-I levels undergo important age-related variations increasing at puberty and decreasing, thereafter, to low levels in the elderly. Low IGF-I levels in the elderly mainly reflect impaired somatotroph secretion but the decline in gonadal sex steroid levels, some protein and micronutrients malnutrition as well as age-dependent variations in IGF-binding proteins may also play a role in the age-related decrease in IGF-I activity. This, in turn, partially accounts for age-related changes in bones, muscles, cardiovascular system, central nervous system and the immune system. However, it is currently unclear whether treatment with exogenous IGF-I can retard or reverse age-related changes in body structure and function. 10.2165/00002512-200016010-00003
    Interaction between malnutrition and ovarian hormones on the systemic IGF-I axis. Goya Luis,García-Segura Luis Miguel,Ramos Sonia,Pascual-Leone Ana María,Argente Jesús,Martín María Angeles,Chowen Julie A European journal of endocrinology OBJECTIVE:In malnutrition both the GH-IGF and reproductive axes are greatly affected. Because the actions of IGF and sex steroids are inter-dependent in many tissues, we have examined how ovariectomy modulates the response of the systemic IGF system to undernutrition. DESIGN AND METHODS:Peripubertal (30 days of age) female rats were either sham operated or ovariectomized. Five days later half of each group was submitted to a protein-caloric restriction diet. All rats were killed at 60 days of age. RESULTS:Growth was decreased in all rats submitted to calorie restriction and this was consistent with a decrease in circulating IGF-I concentrations and liver IGF-I mRNA expression. While in normally fed rats ovariectomy had no significant effect on serum IGF-I concentrations, ovariectomized and underfed rats had significantly higher levels than intact underfed rats. In undernourished rats, serum IGF-binding proteins (IGFBP)-1, -2 and -3 concentrations were significantly reduced and this was not modified by ovariectomy. In contrast, liver mRNA concentrations of IGFBP-1 and -2 were increased and IGFBP-3 unchanged in intact undernourished animals, suggesting that undernutrition could be affecting the proteolysis of these binding proteins, and this response was significantly modulated by ovariectomy. CONCLUSION:These results indicate that the presence of circulating ovarian hormones significantly affects the response of the IGF system to undernutrition.
    The inhibition of growth hormone secretion presented in obesity is not mediated by the high leptin levels: a study in human leptin deficiency patients. Ozata Metin,Dieguez Carlos,Casanueva Felipe F The Journal of clinical endocrinology and metabolism GH secretion is regulated by hypothalamic and peripheral hormones under a very complex interplay. Superimposed on this regulation, signals of a metabolic nature connect GH secretion with the metabolic and energetic homeostasis of a given individual. GH secretion is enhanced in malnutrition and is severely impeded in obesity, but no information is available to explain why GH secretion is severely impeded or blocked in excess adiposity. Obesity is associated with high plasma levels of leptin, and leptin participates at the hypothalamic and pituitary levels in the regulation of GH secretion. Thus, it has been postulated that the inhibitory action of obesity on GH discharge may be mediated by excess leptin levels. The only situation in which obesity does not parallel leptin values is the rare case of morbid obesity due to leptin deficiency caused by missense mutation of the leptin gene. To understand the causes of GH blockade presented in obesity, patients with both homozygous and heterozygous mutations of the leptin gene and matched controls for both sex and body mass index (BMI) were studied. Three homozygous and 5 heterozygous patients with leptin gene mutations as well as 13 control subjects were studied. In all subjects basal levels of leptin and GH values stimulated by the combined administration of GHRH plus GH-releasing peptide-6 (GHRP-6) were analyzed. To analyze the effects of obesity and leptin levels, 5 groups were designed, all them matched by sex and adiposity. The number of subjects (n), leptin levels in micrograms per liter, and adiposity in BMI were as follows: nonobese subjects: n = 5, BMI = 22.1 +/- 0.9 kg/m2, leptin = 5.4 +/- 0.9; heterozygous patients: n = 5, BMI = 27.0 +/- 1.0 kg/m2, leptin = 2.3 +/- 0.1; controls for the heterozygous group: n = 5, BMI = 24.7 +/- 1.1 kg/m2, leptin = 5.7 +/- 1.2; homozygous patients: n = 3, BMI = 54.4 +/- 0.2 kg/m2, leptin = 1.0 +/- 0.2; and controls for the homozygous group: n = 3, BMI = 50.3 +/- 2.0 kg/m2, leptin = 35.0 +/- 6.6. In these matched groups, the GHRH- and GHRP-6-stimulated GH secretion (mean peak +/- SE; micrograms per liter) was: nonobese, 86.8 +/- 8.9 [significantly higher than heterozygous (28.6 +/- 4.9) and control for heterozygous (39.9 +/- 10.4)]; homozygous group, 9.4 +/- 3.0; control for homozygous, 9.3 +/- 1.0 (significantly lower than the heterozygous, control for heterozygous, and nonobese groups). Hence, it appeared that GH discharge was negatively conditioned by adiposity and was not influenced by leptin levels. To further analyze this observation, a correlation analysis showed that GH peaks were negatively correlated with BMI in the 13 control subjects as well as in the 8 leptin-deficient patients. On the contrary, the GH peaks were negatively correlated with leptin levels in controls, but showed the opposite pattern in homo- and heterozygous patients. In conclusion, the GH secretion blockade, which is characteristic of obese states, is due to adiposity or some factor linked to adiposity, but not to elevated plasma leptin levels. 10.1210/jc.2002-020122
    Sexually dimorphic effects of maternal dietary protein restriction on fetal growth and placental expression of 11β-HSD2 in the pig. Shang Yueli,Jia Yimin,Sun Qinwei,Shi Wei,Li Runsheng,Wang Song,Sui Shiyan,Zhao Ruqian Animal reproduction science Placental 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) inactivates glucocorticoids (GCs) to protect fetuses from over-exposure to maternal GCs, yet how maternal malnutrition affects placental 11β-HSD2 expression is unknown. In this study, Meishan sows were fed standard-protein (SP) or low-protein (LP, 50% of SP) diets and fetuses/newborn piglets were weighed and the corresponding placenta and umbilical cord blood were collected on gestational day 70 and the day of parturition. Significant growth retardation was observed in female, but not male, fetuses (P < 0.05) and the newborns (P < 0.01) of the LP group, which was accompanied by sexually dimorphic expression of 11β-HSD2 in placentas. Female fetuses in LP group showed significant decrease in placental 11β-HSD2 protein content (P < 0.05) and enzyme activity (P < 0.05), whereas male fetuses demonstrated significantly enhanced placental 11β-HSD2 activity (P < 0.05). Serum cortisol levels were significantly higher (P < 0.05) in male piglets compared to females, and the effects of maternal protein restriction on thyroid hormones (T3 and T4) in the umbilical cord blood were also sex dimorphic. Male piglets in LP group had significantly higher T3 (P < 0.01) and lower T4 (P < 0.01), whereas female piglets showed significantly lower T4 (P < 0.01) with no change in T3. As a result, male piglets in LP group exhibited significantly higher T3/T4 ratio compared to female counterparts. These results indicate that the effects of maternal protein restriction on placental 11β-HSD2 expression are gender-dependent in the pig, and thyroid hormones may be involved in such effects. 10.1016/j.anireprosci.2015.07.001
    Adrenocorticosteroids and corticosteroid binding globulins in protein calorie malnutrition. Samuel A M,Kadival G V,Patel B D,Desai A G The American journal of clinical nutrition A study of adrenocorticosteroids and corticosteroid binding globulins was undertaken in 35 malnourished children with a weight deficit of 10 to 45%. The mean corticosteroid levels 5.9 +/- 3.0 mug% were not significantly different from control values of 6.43 +/- 3.2 mug%. Steroid levels were however low (4.38 +/- 1.8 mug%) in children with marasmic kwashiorkor. The corticosteroid binding globulin was reduced to 11.9 +/- 5.4 mug of cortisol bound in malnourished children with and without edema and was significantly lower than controls. "Free cortisol" levels were significantly raised in the malnourished state. In the presence of acute infection there was a remarkable rise of steroids suggesting that there was no hypofunction of the adrenal cortex. Where the infection was chronic (e.g., pulmonary tuberculosis) the levels were normal suggesting an adaptation to the stress. Early studies of the steroids and corticosteroid binding globulins within 2 to 3 weeks of starting a high protein diet showed that there was a remarkable rise of serum albumin 2.3 +/- 0.4 to 3.3 +/- 0.7 g%, steroids from 5.9 +/- 5.5 to 12.3 +/- 7.4 and corticosteroid binding globulins from 13.0 +/- 4.1 to 20.2 +/- 6.3 mug of cortisol bound per 100 ml. Weight gain was from 0.2 to 1.0 kg. A follow-up of four children for 6 weeks showed that the steroid levels fell to within normal limits. The integrity of the hypothalamohypophyseal adrenal axis was unimpaired in five out of six children studied. In conclusion it appears that marasmic children are well adapted to the stress of malnutrition and the ability of the adrenals to respond to stress is unimpaired. 10.1093/ajcn/29.8.889
    An enzyme immunoassay for salmon gonadotropin-releasing hormone and its application to the study of the effects of diet on brain and pituitary GnRH in the sea bass, Dicentrarchus labrax. Kah O,Zanuy S,Pradelles P,Cerdà J L,Carrillo M General and comparative endocrinology The effects of two different diets [diet 1 (D1), high protein-low carbohydrate; diet 2 (D2), low protein-high carbohydrate] on brain and pituitary gonadotropin-releasing hormone (GnRH) contents, as well as circulating steroids and vitellogenin, were studied over the reproductive period of the sea bass. Salmon GnRH was measured using a newly developed competitive enzyme immunoassay with an enzymatic tracer made of sGnRH covalently coupled to acetylcholinesterase from the electric organ of the eel Electrophorus electricus. The pituitary GnRH content of animals of both sexes fed D1 was significantly reduced at the time of spawning compared with the pre- and postspawning stages, whereas fish fed D2 did not exhibit such changes. In the brain only minor differences in the GnRH content were observed between the two diets. It is concluded that GnRH release rather than synthesis is affected in fish fed a low protein-high carbohydrate regimen. Plasma sex steroids and vitellogenin were not greatly affected by the diet. 10.1006/gcen.1994.1146
    Influence of Low Protein Diet-Induced Fetal Growth Restriction on the Neuroplacental Corticosterone Axis in the Rat. Schmidt Marius,Rauh Manfred,Schmid Matthias C,Huebner Hanna,Ruebner Matthias,Wachtveitl Rainer,Cordasic Nada,Rascher Wolfgang,Menendez-Castro Carlos,Hartner Andrea,Fahlbusch Fabian B Frontiers in endocrinology Placental steroid metabolism is linked to the fetal hypothalamus-pituitary-adrenal axis. Intrauterine growth restriction (IUGR) might alter this cross-talk and lead to maternal stress, in turn contributing to the pathogenesis of anxiety-related disorders of the offspring, which might be mediated by fetal overexposure to, or a reduced local enzymatic protection against maternal glucocorticoids. So far, direct evidence of altered levels of circulating/local glucocorticoids is scarce. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) allows quantitative endocrine assessment of blood and tissue. Using a rat model of maternal protein restriction (low protein [LP] vs. normal protein [NP]) to induce IUGR, we analyzed fetal and maternal steroid levels via LC-MS/MS along with the local expression of 11beta-hydroxysteroid-dehydrogenase (). Pregnant Wistar dams were fed a low protein (8%, LP; IUGR) or an isocaloric normal protein diet (17%, NP; controls). At E18.5, the expression of and was determined by RT-PCR in fetal placenta and brain. Steroid profiling of maternal and fetal whole blood, fetal brain, and placenta was performed via LC-MS/MS. In animals with LP-induced reduced body ( < 0.001) and placental weights ( < 0.05) we did not observe any difference in the expressional -ratio in brain or placenta. Moreover, LP diet did not alter corticosterone (Cort) or 11-dehydrocorticosterone (DH-Cort) levels in dams, while fetal whole blood levels of Cort were significantly lower in the LP group ( < 0.001) and concomitantly in LP brain ( = 0.003) and LP placenta ( = 0.002). Maternal and fetal progesterone levels (whole blood and tissue) were not influenced by LP diet. Various rat models of intrauterine stress show profound alterations in placental Hsd11b2 gatekeeper function and fetal overexposure to corticosterone. In contrast, LP diet in our model induced IUGR without altering maternal steroid levels or placental enzymatic glucocorticoid barrier function. In fact, IUGR offspring showed significantly reduced levels of circulating and local corticosterone. Thus, our LP model might not represent a genuine model of intrauterine stress. Hypothetically, the observed changes might reflect a fetal attempt to maintain anabolic conditions in the light of protein restriction to sustain regular brain development. This may contribute to fetal origins of later neurodevelopmental sequelae. 10.3389/fendo.2019.00124
    Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women. Bihuniak Jessica D,Sullivan Rebecca R,Simpson Christine A,Caseria Donna M,Huedo-Medina Tania B,O'Brien Kimberly O,Kerstetter Jane E,Insogna Karl L The Journal of nutrition Increasing dietary protein within a physiologic range stimulates intestinal calcium absorption, but it is not known if specific amino acids or dietary protein as a whole are responsible for this effect. Therefore, we selectively supplemented a low-protein (0.7 g/kg) diet with either the calcium-sensing receptor-activating amino acids (CaSR-AAAs) L-tryptophan, L-phenylalanine, and L-histidine, or the dibasic amino acids (DAAs) L-arginine and L-lysine, to achieve intakes comparable to the content of a high-protein diet (2.1 g/kg) and measured intestinal calcium absorption. Fourteen young women took part in a placebo-controlled, double-blind, crossover feeding trial in which each participant ingested a 6-d low-protein diet supplemented with CaSR-AAAs, DAAs, or methylcellulose capsules (control) after an 11-d adjustment period. All participants ingested all 3 diets in random order. Intestinal calcium absorption was measured between days 5 and 6 using dual-stable calcium isotopes ((42)Ca, (43)Ca, and (44)Ca). There was no difference in calcium absorption between the diet supplemented with CaSR-AAAs (22.9 ± 2.0%) and the control diet (22.3 ± 1.4%) (P = 0.64). However, calcium absorption tended to be greater during the DAA supplementation period (25.2 ± 1.4%) compared with the control diet period (22.3 ± 1.4%) (P < 0.10). Larger and longer clinical trials are needed to clarify the possible benefit of arginine and lysine on calcium absorption. 10.3945/jn.113.185009
    Dietary phosphorus restriction by a standard low-protein diet decreased serum fibroblast growth factor 23 levels in patients with early and advanced stage chronic kidney disease. Goto Shunsuke,Nakai Kentaro,Kono Keiji,Yonekura Yuriko,Ito Jun,Fujii Hideki,Nishi Shinichi Clinical and experimental nephrology BACKGROUND:Elevated serum fibroblast growth factor 23 (FGF23) levels are associated with mortality, cardiovascular disease, and disease progression in patients with chronic kidney disease (CKD). Although recent studies demonstrated that FGF23 levels decreased in response to dietary restriction of phosphorus and/or use of phosphate binders, research on the effects of a standard low-protein diet is lacking. METHODS:The effects of a standard low-protein diet on serum FGF23, intact parathyroid hormone, and 1,25-dihydroxyvitamin D levels were investigated in patients with early (n = 15) and advanced (n = 20) CKD. RESULTS:Serum FGF23 levels decreased in both groups. Changes in FGF23 levels correlated with changes in 24 h urinary phosphorus excretion in the advanced CKD group. Decreased serum intact parathyroid hormone levels were observed only in the advanced CKD group and increased serum 1,25-dihydroxyvitamin D levels only in the early CKD group. CONCLUSIONS:These findings suggest that consuming standard low-protein diet decreased serum FGF23 levels in patients with CKD. Serum FGF23 levels may therefore be a useful marker to monitor the effects of a low-protein diet in early and advanced stage CKD. 10.1007/s10157-014-0947-4
    Accelerated aging of reproductive capacity in male rat offspring of protein-restricted mothers is associated with increased testicular and sperm oxidative stress. Rodríguez-González Guadalupe L,Reyes-Castro Luis A,Vega Claudia C,Boeck Lourdes,Ibáñez Carlos,Nathanielsz Peter W,Larrea Fernando,Zambrano Elena Age (Dordrecht, Netherlands) Maternal protein restriction (MPR) in pregnancy causes life course organ dysfunction, but few studies link the developmental origins of disease hypothesis to early aging. Suboptimal developmental nutrition increases oxidative stress (OS) and male infertility, damaging sperm function. We hypothesized that MPR in pregnancy accelerates age-related changes in testicular and sperm function related to both maternal diet and increased testicular OS in rat offspring. We studied male rats whose pregnant mothers ate either control (C, 20 % casein) or restricted (R, 10 % casein) isocaloric diet. After birth, mothers and offspring ate C diet. Testes were retrieved at 19 days gestation and across the life course (postnatal day (PND) 21, 36, 110, and 850) to measure OS markers, antioxidant enzymes, serum FSH, LH, and testosterone, and PND 110 sperm OS and quality. Fertility rate was evaluated at PND 110, 450, and 850. Offspring showed age- and MPR-related changes in testosterone, testicular OS markers and antioxidant enzymes and fertility, and maternal diet-related OS and sperm antioxidant enzyme changes. Developmental programming is considered a key factor in predisposing to chronic disease. Our data show that programming also plays an important role in aging trajectory. This interaction is a little studied area in aging biology that merits more investigation. 10.1007/s11357-014-9721-5
    The interactive effect of dietary protein and vitamin levels on the depression of gonadal development in growing male rats kept under disturbed daily rhythm. Hanai Miho,Esashi Takatoshi Journal of nutritional science and vitaminology The purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. The present study examined protein and vitamins, and their interactions. This study was based on three-way ANOVA; the three factors were lighting conditions, dietary protein and dietary vitamins, respectively. The levels of dietary protein were low or normal: 9% casein or 20% casein. The levels of dietary vitamins were low, normal or high: 1/3.3 of normal (AIN-93G diet) content, normal content, or three times the normal content, respectively. Other compositions were the same as those of the AIN-93G diet, and six kinds of experimental diet were prepared. Four-week-old rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle) for 4 wk. After 4 wk, the gonadal weights and serum testosterone content were evaluated. In the constant darkness groups (D-groups), the low-protein diet induced reduction of gonadal organ weights and serum testosterone concentrations. This reduction of gonadal organ weights was exacerbated by progressively higher levels of dietary vitamins. In the case of a normal-protein diet, the depression of gonadal development was not accelerated by high-vitamin intake. In the normal lighting groups (N-groups), the low-protein and high-vitamin diet slightly depressed gonadal development. These results suggest that the metabolism of protein and vitamins is different in rats being kept under constant darkness, and that excess dietary vitamins have an adverse effect on gonadal development in rats fed a low-protein diet.
    Blood profile of proteins and steroid hormones predicts weight change after weight loss with interactions of dietary protein level and glycemic index. Wang Ping,Holst Claus,Andersen Malene R,Astrup Arne,Bouwman Freek G,van Otterdijk Sanne,Wodzig Will K W H,van Baak Marleen A,Larsen Thomas M,Jebb Susan A,Kafatos Anthony,Pfeiffer Andreas F H,Martinez J Alfredo,Handjieva-Darlenska Teodora,Kunesova Marie,Saris Wim H M,Mariman Edwin C M PloS one BACKGROUND:Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance. OBJECTIVE:To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study. DESIGN:Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured. RESULTS:Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%. CONCLUSIONS:A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss. REGISTRATION:ClinicalTrials.gov NCT00390637. 10.1371/journal.pone.0016773
    Human sex hormone-binding globulin does not provide metabolic protection against diet-induced obesity and dysglycemia in mice. Sofer Yael,Nevo Nava,Vechoropoulos Michal,Shefer Gabi,Osher Etty,Landis Nathan,Tordjman Karen,Hammond Geoffrey L,Stern Naftali Endocrine connections BACKGROUND:Sex hormone-binding globulin (SHBG) is the main transporter of sex hormones in most vertebrates. Low SHBG levels have been linked to increased risk for diabetes and metabolic syndrome. Polymorphisms of the gene linked to low SHBG protein levels also strongly predicted increased risk of type 2 diabetes, thus raising the possibility that SHBG may play a role in the pathogenesis of insulin resistance and diabetes. AIM:To examine whether expression of human in mice may ameliorate the development of diabetes and metabolic syndrome in response to a high-fat diet (HFD). METHODS:Transgene mice expressing a human transgene () ( = 10/11; males/females) and their wild type littermates ( = 12/8; males/females) were fed HFD for 4.5 months. RESULTS:HFD induced comparable obesity in control and mice. Male transgenes had higher muscle mass after 2-3.5 months HFD (0.43 ± 0.028 ( = 4) vs 0.38 ± 0.053 g ( = 7),  = 0.05). Fasting blood glucose, as well as insulin or HOMA-IR, was not different in transgenic vs wild-type males after 4-5 months HFD. Female transgenes had higher fasting glucose (152 ± 29 ( = 7) vs 115 ± 27 mg/dL,  = 0.01 ( = 8)), but mean insulin and HOMA-IR were not different. Likewise, insulin tolerance test and intra-peritoneal glucose tolerance test (GTT) were not different. Finally, + mice were not different from controls in terms of liver enzymes, serum triglyceride levels and blood pressure. CONCLUSION:In mice with diet-induced obesity, human did not protect against development of obesity or dysglycemia. 10.1530/EC-17-0240
    Maternal protein restriction during gestation and lactation programs offspring ovarian steroidogenesis and folliculogenesis in the prepubertal gilts. Sui Shiyan,He Bin,Jia Yimin,Li Runsheng,Cai Demin,Li Xi,Song Haogang,Jia Longfei,Zhao Ruqian The Journal of steroid biochemistry and molecular biology Maternal malnutrition may disrupt ovarian functions in adult offspring. Steroidogenesis and folliculogenesis in the offspring ovary appear to be the major targets of nutritional programming. Nevertheless, the mechanism by which maternal low-protein diet affects the offspring steroidogenesis and folliculogenesis, and the possible pathway linking these two processes remain unclear. In this study, Landrace×Yorkshire crossbred sows were fed either standard (SP) or low-protein (LP, 50% of the SP) diets throughout gestation and lactation. Female offspring were fed the same diet after weaning until 6 months of age. LP offspring had higher serum 17β-estradiol level (P<0.01), which was accompanied by lower mRNA (P<0.05) but higher protein (P<0.05) expression of cytochrome P450 aromatase (CYP19A1) in the ovary. CYP19A1 protein up-regulation was associated with lower ovarian expression of drosha (P<0.05) and miRNAs targeting CYP19A1 (P<0.05). LP offspring had less graafian follicles with more apoptotic granulosa cells (P<0.05), as well as higher caspase 3 activity (P<0.05) and FasL expression (P<0.05) in the ovary. FasL gene up-regulation was associated with higher ERα protein expression (P<0.05) and binding to FasL gene promoter. These results suggest that a maternal LP diet in pregnancy and lactation elevated serum 17β-estradiol level by activating CYP19A1 through miRNA-mediated mechanism, and induced granulosa apoptosis in graafian follicles through ER-activated Fas/FasL-caspase 3 pathway. 10.1016/j.jsbmb.2014.04.010
    Protein restoration in low-birth-weight rat offspring derived from maternal low-protein diet leads to elevated hepatic CYP3A and CYP2C11 activity in adulthood. Sohi Gurjeev,Barry Eric J,Velenosi Thomas J,Urquhart Bradley L,Hardy Daniel B Drug metabolism and disposition: the biological fate of chemicals The World Health Organization has identified hypercholesterolemia to be one of the major symptoms encompassing the metabolic syndrome. Moreover, epidemiologic evidence indicates that low-birth-weight offspring are at greater risk of developing the metabolic syndrome. Previous work in our laboratory demonstrated that maternal protein restriction (MPR) results in impaired fetal growth and hypercholesterolemia in adulthood. This was attributed to repression of hepatic CYP7A1, a rate-limiting enzyme that catabolizes cholesterol to bile acids. Another important function of hepatic cytochrome P450 enzymes is the phase I oxidative metabolism of drugs (i.e., statins for hypercholesterolemia), which can significantly impact pharmacokinetics. We hypothesized that MPR offspring may have altered ability to metabolize drugs in adulthood. To address this hypothesis, we maintained Wistar rats on a 20% protein diet (control) or a low 8% protein diet throughout prenatal and postnatal life (LP1) or exclusively during prenatal life and weaning (LP2). Intriguingly CYP3A and CYP2C11 intrinsic clearance (Vmax/Km) was significantly increased exclusively in LP2 offspring at postnatal day 130 compared with control or LP1 offspring, as evaluated by testosterone enzyme kinetics in liver microsomes. The increase in activity was secondary to an increase in CYP3A23 and CYP2C11 mRNA. Collectively, these findings suggest that a low-birth-weight offspring with postnatal catch-up growth may have a diminished response to xenobiotics metabolized by CYP3A and CYP2C11 enzymes. 10.1124/dmd.113.053538
    Comparative morphophysiological evaluation of the testis of adult Wistar rats fed low protein-energy diet and dosed with aqueous extracts of Cuscuta australis. Ozegbe P C,Omirinde J O Nigerian journal of physiological sciences : official publication of the Physiological Society of Nigeria Cuscuta australis (C. australis) seed and stem are historically used by the local population as dietary supplement for the management of infertility. This study, therefore, evaluated the effect of orally administered aqueous extracts of C. australis seed and stem, 300 mg/kg body weight/day for seven days, on the testis of the adult Wistar rat fed either low or normal protein-energy diets. The control group received water. The relative weight of the testis was non-significantly increased (p>0.05) in the Low Protein-energy diet-Water-treated (LPWA), Low Protein-energy diet-Seed-treated (LPSE) and Normal Protein-energy diet-Seed-treated (NPSE) groups relative to the Normal Protein-energy diet-Water-treated (NPWA). The weight of the testis was also non-significantly increased (p˃0.05) in the Low Protein-energy diet-Stem-treated (LPST), but decreased in the Normal Protein-energy diet-Stem-treated (NPST), relative to LPWA and NPWA. Heights of germinal epithelium were significantly decreased (p<0.05) in the LPWA, LPSE and LPST relative to the NPWA, NPSE and NPST. Diet significantly influenced (p<0.001) the effect of stem extract on the height of germinal epithelium. The NPSE, LPSE, NPST, LPST and LPWA showed significantly decreased (p<0.001) plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) relative to NPWA. The LPWA, LPSE and NPST also showed significantly decreased (p<0.001) levels of testosterone relative to NPWA and LPST. Diet significantly influenced (p<0.001) the effect of seed on the level of LH. Seed-diet interactions significantly affected the levels of FSH (p<0.001) and LH (p<0.05), but not testosterone. Diet significantly influenced (p<0.001) the effects of stem extract on the levels of FSH, LH and testosterone. Stem-diet interactions significantly affected (p<0.001) the levels of FSH, LH and testosterone. Our data suggest that the aqueous extract of C. australis stem is more potent than the seed extract and that dietary protein-energy intake may influence the efficacy of orally administered aqueous extracts of C. australis.
    A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development. Zambrano E,Rodríguez-González G L,Guzmán C,García-Becerra R,Boeck L,Díaz L,Menjivar M,Larrea F,Nathanielsz P W The Journal of physiology Nutrient restriction during pregnancy and lactation impairs growth and development. Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. We determined effects of maternal protein restriction (50% control protein intake) during fetal development and/or lactation in rats on the reproductive system of male progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups: CC, RR, CR and RC. We report findings in male offspring only. Maternal protein restriction increased maternal serum corticosterone, oestradiol and testosterone (T) concentrations at 19 days gestation. Pup birth weight was unchanged but ano-genital distance was increased by maternal protein restriction (P < 0.05). Testicular descent was delayed 4.4 days in RR, 2.1 days in CR and 2.2 days in RC and was not related to body weight. Body weight and testis weight were reduced in RR and CR groups at all ages with the exception of CR testis weight at 270 days postnatal age (PN). At 70 days PN luteinizing hormone and T concentrations were reduced in RR, CR and RC. mRNA for P450 side chain cleavage (P450scc) was reduced in RR and CR at 21 days PN but was unchanged at 70 days PN. Fertility rate was reduced at 270 days PN in RC and sperm count in RR and RC. We conclude that maternal protein delays sexual maturation in male rats and that some effects only emerge in later life. 10.1113/jphysiol.2004.078543
    Regulation of branched-chain amino acid catabolism: nutritional and hormonal regulation of activity and expression of the branched-chain alpha-keto acid dehydrogenase kinase. Shimomura Y,Obayashi M,Murakami T,Harris R A Current opinion in clinical nutrition and metabolic care Branched-chain alpha-keto acid dehydrogenase kinase is responsible for the inactivation and phosphorylation of the branched-chain alpha-keto acid dehydrogenase complex, the enzyme that catalyses the committed step of branched-chain amino acid catabolism. The activity of the branched-chain alpha-keto acid dehydrogenase complex is inversely correlated with kinase activity, suggesting that the relative activity of the kinase is the primary regulator of the activity of the complex. It has been shown that kinase activity and expression are affected by nutritional states imposed by low-protein diet feeding, starvation, diabetes, and exercise. Evidence has also been presented that certain hormones, particularly insulin, glucocorticoid, thyroid hormone and female sex hormones, affect the activity and expression of the kinase. The findings indicate that nutritional and hormonal control of the activity and expression of branched-chain alpha-keto acid dehydrogenase kinase provides an important means of control of the activity of the branched-chain alpha-keto acid dehydrogenase complex, with inactivation serving to conserve branched-chain amino acids for protein synthesis in some situations and activation serving to provide carbon for gluconeogenesis in others. 10.1097/00075197-200109000-00013
    Supplementation of Diet With Galacto-oligosaccharides Increases Bifidobacteria, but Not Insulin Sensitivity, in Obese Prediabetic Individuals. Canfora Emanuel E,van der Beek Christina M,Hermes Gerben D A,Goossens Gijs H,Jocken Johan W E,Holst Jens J,van Eijk Hans M,Venema Koen,Smidt Hauke,Zoetendal Erwin G,Dejong Cornelis H C,Lenaerts Kaatje,Blaak Ellen E Gastroenterology BACKGROUND & AIMS:The gut microbiota affects host lipid and glucose metabolism, satiety, and chronic low-grade inflammation to contribute to obesity and type 2 diabetes. Fermentation end products, in particular the short-chain fatty acid (SCFA) acetate, are believed to be involved in these processes. We investigated the long-term effects of supplementation with galacto-oligosaccharides (GOS), an acetogenic fiber, on the composition of the human gut microbiota and human metabolism. METHODS:We performed a double-blinded, placebo-controlled, parallel intervention study of 44 overweight or obese (body mass index, 28-40 kg/m) prediabetic men and women (ages, 45-70 y) from October 2014 through October 2015 in Maastricht, The Netherlands. The participants were assigned randomly to groups who ingested 15 g GOS or isocaloric placebo (maltodextrin) daily with their regular meals for 12 weeks. Before and after this period, we collected data on peripheral and adipose tissue insulin sensitivity, fecal microbiota composition, plasma and fecal SCFA, energy expenditure and substrate oxidation, body composition, and hormonal and inflammatory responses. The primary outcome was the effect of GOS on peripheral insulin sensitivity, measured by the hyperinsulinemic-euglycemic clamp method. RESULTS:Supplementation of diets with GOS, but not placebo, increased the abundance of Bifidobacterium species in feces by 5-fold (P = .009; q = 0.144). Microbial richness or diversity in fecal samples were not affected. We did not observe any differences in fecal or fasting plasma SCFA concentrations or in systemic concentrations of gut-derived hormones, incretins, lipopolysaccharide-binding protein, or other markers of inflammation. In addition, no significant alterations in peripheral and adipose tissue insulin sensitivity, body composition, and energy and substrate metabolism were found. CONCLUSIONS:Twelve-week supplementation of GOS selectively increased fecal Bifidobacterium species abundance, but this did not produce significant changes in insulin sensitivity or related substrate and energy metabolism in overweight or obese prediabetic men and women. ClincialTrials.gov number, NCT02271776. 10.1053/j.gastro.2017.03.051
    Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Boden Guenther,Sargrad Karin,Homko Carol,Mozzoli Maria,Stein T Peter Annals of internal medicine BACKGROUND:It is not known how a low-carbohydrate, high-protein, high-fat diet causes weight loss or how it affects blood glucose levels in patients with type 2 diabetes. OBJECTIVE:To determine effects of a strict low-carbohydrate diet on body weight, body water, energy intake and expenditure, glycemic control, insulin sensitivity, and lipid levels in obese patients with type 2 diabetes. DESIGN:Inpatient comparison of 2 diets. SETTING:General clinical research center of a university hospital. PATIENTS:10 obese patients with type 2 diabetes. INTERVENTION:Usual diets for 7 days followed by a low-carbohydrate diet for 14 days. MEASUREMENTS:Body weight, water, and composition; energy intake and expenditure; diet satisfaction; hemoglobin A1c; insulin sensitivity; 24-hour urinary ketone excretion; and plasma profiles of glucose, insulin, leptin, and ghrelin. RESULTS:On the low-carbohydrate diet, mean energy intake decreased from 3111 kcal/d to 2164 kcal/d. The mean energy deficit of 1027 kcal/d (median, 737 kcal/d) completely accounted for the weight loss of 1.65 kg in 14 days (median, 1.34 kg in 14 days). Mean 24-hour plasma profiles of glucose levels normalized, mean hemoglobin A1c decreased from 7.3% to 6.8%, and insulin sensitivity improved by approximately 75%. Mean plasma triglyceride and cholesterol levels decreased (change, -35% and -10%, respectively). LIMITATIONS:The study was limited by the short duration, small number of participants, and lack of a strict control group. CONCLUSION:In a small group of obese patients with type 2 diabetes, a low-carbohydrate diet followed for 2 weeks resulted in spontaneous reduction in energy intake to a level appropriate to their height; weight loss that was completely accounted for by reduced caloric intake; much improved 24-hour blood glucose profiles, insulin sensitivity, and hemoglobin A1c; and decreased plasma triglyceride and cholesterol levels. The long-term effects of this diet, however, remain uncertain. 10.7326/0003-4819-142-6-200503150-00006
    Effects of low-carbohydrate and low-fat diets: a randomized trial. Bazzano Lydia A,Hu Tian,Reynolds Kristi,Yao Lu,Bunol Calynn,Liu Yanxi,Chen Chung-Shiuan,Klag Michael J,Whelton Paul K,He Jiang Annals of internal medicine BACKGROUND:Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations. OBJECTIVE:To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors. DESIGN:A randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271). SETTING:A large academic medical center. PARTICIPANTS:148 men and women without clinical cardiovascular disease and diabetes. INTERVENTION:A low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial. MEASUREMENTS:Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months. RESULTS:Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, -3.5 kg [95% CI, -5.6 to -1.4 kg]; P = 0.002), fat mass (mean difference in change, -1.5% [CI, -2.6% to -0.4%]; P = 0.011), ratio of total-high-density lipoprotein (HDL) cholesterol (mean difference in change, -0.44 [CI, -0.71 to -0.16]; P = 0.002), and triglyceride level (mean difference in change, -0.16 mmol/L [-14.1 mg/dL] [CI, -0.31 to -0.01 mmol/L {-27.4 to -0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet. LIMITATION:Lack of clinical cardiovascular disease end points. CONCLUSION:The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors. PRIMARY FUNDING SOURCE:National Institutes of Health. 10.7326/M14-0180
    Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. Ebbeling Cara B,Feldman Henry A,Klein Gloria L,Wong Julia M W,Bielak Lisa,Steltz Sarah K,Luoto Patricia K,Wolfe Robert R,Wong William W,Ludwig David S BMJ (Clinical research ed.) OBJECTIVE:To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure. DESIGN:Randomized trial. SETTING:Multicenter collaboration at US two sites, August 2014 to May 2017. PARTICIPANTS:164 adults aged 18-65 years with a body mass index of 25 or more. INTERVENTIONS:After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose). MAIN OUTCOME MEASURES:The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin. RESULTS:Total energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval -29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (-6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol). CONCLUSIONS:Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion. TRIAL REGISTRATION:ClinicalTrials.gov NCT02068885. 10.1136/bmj.k4583
    Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Levine Morgan E,Suarez Jorge A,Brandhorst Sebastian,Balasubramanian Priya,Cheng Chia-Wei,Madia Federica,Fontana Luigi,Mirisola Mario G,Guevara-Aguirre Jaime,Wan Junxiang,Passarino Giuseppe,Kennedy Brian K,Wei Min,Cohen Pinchas,Crimmins Eileen M,Longo Valter D Cell metabolism Mice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50-65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect of high protein intake and GHR-IGF-1 signaling on the incidence and progression of breast and melanoma tumors, but also the detrimental effects of a low protein diet in the very old. These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity. 10.1016/j.cmet.2014.02.006
    Homeostatic sensing of dietary protein restriction: A case for FGF21. Hill Cristal M,Berthoud Hans-Rudolf,Münzberg Heike,Morrison Christopher D Frontiers in neuroendocrinology Restriction of dietary protein intake increases food intake and energy expenditure, reduces growth, and alters amino acid, lipid, and glucose metabolism. While these responses suggest that animals 'sense' variations in amino acid consumption, the basic physiological mechanism mediating the adaptive response to protein restriction has been largely undescribed. In this review we make the case that the liver-derived metabolic hormone FGF21 is the key signal which communicates and coordinates the homeostatic response to dietary protein restriction. Support for this model centers on the evidence that FGF21 is induced by the restriction of dietary protein or amino acid intake and is required for adaptive changes in metabolism and behavior. FGF21 occupies a unique endocrine niche, being induced when energy intake is adequate but protein and carbohydrate are imbalanced. Collectively, the evidence thus suggests that FGF21 is the first known endocrine signal of dietary protein restriction. 10.1016/j.yfrne.2018.06.002
    Are high-protein, vegetable-based diets safe for kidney function? A review of the literature. Bernstein Adam M,Treyzon Leo,Li Zhaoping Journal of the American Dietetic Association In individuals with chronic kidney disease, high-protein diets have been shown to accelerate renal deterioration, whereas low-protein diets increase the risk of protein malnutrition. Vegetarian diets have been promoted as a way to halt progression of kidney disease while maintaining adequate nutrition. We review the literature to date comparing the effects of animal and vegetable protein on kidney function in health and disease. Diets with conventional amounts of protein, as well as high-protein diets, are reviewed. The literature shows that in short-term clinical trials, animal protein causes dynamic effects on renal function, whereas egg white, dairy, and soy do not. These differences are seen both in diets with conventional amounts of protein and those with high amounts of protein. The long-term effects of animal protein on normal kidney function are not known. Although data on persons with chronic kidney disease are limited, it appears that high intake of animal and vegetable proteins accelerates the underlying disease process not only in physiologic studies but also in short-term interventional trials. The long-term effects of high protein intake on chronic kidney disease are still poorly understood. Several mechanisms have been suggested to explain the different effects of animal and vegetable proteins on normal kidney function, including differences in postprandial circulating hormones, sites of protein metabolism, and interaction with accompanying micronutrients. 10.1016/j.jada.2007.01.002
    Low protein intake: the impact on calcium and bone homeostasis in humans. Kerstetter Jane E,O'Brien Kimberly O,Insogna Karl L The Journal of nutrition Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both. 10.1093/jn/133.3.855S
    Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis. Santesso N,Akl E A,Bianchi M,Mente A,Mustafa R,Heels-Ansdell D,Schünemann H J European journal of clinical nutrition BACKGROUND/OBJECTIVES:Numerous randomised controlled trials (RCTs) published in first tier medical journals have evaluated the health effects of diets high in protein. We conducted a rigorous systematic review of RCTs comparing higher- and lower-protein diets. METHODS:We searched several electronic databases up to July 2011 for studies focusing on patient-important outcomes (for example, cardiovascular disease) and secondary outcomes such as risk factors for chronic disease (for example, adiposity). RESULTS:We identified 111 articles reporting on 74 trials. Pooled effect sizes using standardised mean differences (SMDs) were small to moderate and favoured higher-protein diets for weight loss (SMD -0.36, 95% confidence interval (CI) -0.56 to -0.17), body mass index (-0.37, CI -0.56 to 0.19), waist circumference (-0.43, CI -0.69 to -0.16), blood pressure (systolic: -0.21, CI -0.32 to -0.09 and diastolic: -0.18, CI -0.29 to -0.06), high-density lipoproteins (HDL 0.25, CI 0.07 to 0.44), fasting insulin (-0.20, CI -0.39 to -0.01) and triglycerides (-0.51, CI -0.78 to -0.24). Sensitivity analysis of studies with lower risk of bias abolished the effect on HDL and fasting insulin, and reduced the effect on triglycerides. We observed nonsignificant effects on total cholesterol, low-density lipoproteins, C-reactive protein, HbA1c, fasting blood glucose, and surrogates for bone and kidney health. Adverse gastrointestinal events were more common with high-protein diets. Multivariable meta-regression analysis showed no significant dose response with higher protein intake. CONCLUSIONS:Higher-protein diets probably improve adiposity, blood pressure and triglyceride levels, but these effects are small and need to be weighed against the potential for harms. 10.1038/ejcn.2012.37
    Control of protein and energy intake - brain mechanisms. Davidenko O,Darcel N,Fromentin G,Tomé D European journal of clinical nutrition The protein content of the diet has long been investigated for its influence on food behavior. High-protein diets promote satiety and reduce calorie intake, whereas results for low-protein diets are more contradictory and less established. Protein sensing might take place in the oral cavity or in the post-oral gastrointestinal tract, where specific receptors have been found. Protein signaling to the brain may act through the vagal nerve and involve gastric hormones, such as cholecystokinin and peptide YY. Other pathways are post-absorptive signaling and the direct influence of brain levels of amino acids. High-protein diet enhances the activity of brain satiety centers, mainly the nucleus of the solitary tract and arcuate nucleus, although the activity of brain reward centers might also be modified. A better understanding of the role of both homeostatic and hedonic systems is needed to fully describe the influence of protein on food intake. 10.1038/ejcn.2013.73
    Effects of Dietary Protein on Thyroid Axis Activity. Pałkowska-Goździk Ewelina,Lachowicz Katarzyna,Rosołowska-Huszcz Danuta Nutrients Thyroid hormones (TH) are essential for the normal development and function of every vertebrate. The hypothalamic-pituitary-thyroid (HPT) axis is regulated to maintain euthyroid status. One of the most influential environmental factors that determines HPT axis activity is nutrition. Both food availability and substrate diversity affect thyroid hormone economy. The present paper aims to summarize literature data concerning the influence of the amount and the type of protein on thyroid axis activity. This review sheds light on the contribution of a low-protein diet or insufficient intake of essential amino acids to TH abnormalities. We believe that the knowledge of these dependencies could improve the results of nutritional interventions in thyroid axis disorders and enhance the efficiency of animal breeding. 10.3390/nu10010005
    Endocrine pancreas development: effects of metabolic and intergenerational programming caused by a protein-restricted diet. Frantz Eliete Dalla Corte,Peixoto-Silva Nayara,Pinheiro-Mulder Alessandra Pancreas Experimental studies have demonstrated an association between low birth weight and the later development of type 2 diabetes. This association could be a result of the programming process that affects pancreatic beta-cell development due to poor fetal nutrition. This mechanism may not be limited to the first generation. In rodents, endocrine cells of the pancreas are derived from cells of the endodermal dorsal and ventral anlage that migrate and gather in clusters in a process termed isletogenesis. Islet development occurs relatively late in gestation, and islets undergo substantial remodeling immediately after birth under the regulation of a transcription factor network. Furthermore, the offspring of mice fed a protein-restricted diet exhibit a reduced pancreatic beta-cell mass at birth, lower vascularization, increased apoptosis rate, and changes in glucose metabolism in later life. Although the mechanisms underlying these relationships are unclear, it has been hypothesized that in utero nutritional conditions affect epigenetic patterns of gene transcription that persist throughout life and subsequent generations. We aimed to review the process of the formation of the endocrine pancreas in rodents, the consequences of a protein-restricted diet on offspring, and the transgenerational effects of this insult on the incidence of type 2 diabetes. 10.1097/MPA.0b013e3182236320
    [Objectives of the low-protein diet]. Brunori G Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia The prescription of low-protein diets to patients with chronic kidney disease has several objectives: to lower the dietary phosphorus load and circulating phosphorus and parathyroid hormone levels, and to improve the acid-base control and uremic symptoms while preserving the nutritional status. However, such objectives are always subordinate to the necessity of maintaining adequate calorie intake. An important target of any reduction of dietary protein intake is the delay of renal death and start of dialysis, as demonstrated by several methodologically sound studies and meta-analyses. However, no prospective study has yet confirmed the nephroprotective potential of low-protein diets repeatedly shown in animal models. Such negative results in human studies could be explained by their frequent methodological flaws, as well as by the modest actual reduction of protein intake compared with pre-study levels. The recent Cochrane meta-analysis confirmed that reducing dietary protein intake can delay renal death and dialysis. The Number-to-Treat estimate in the Cochrane meta-analysis (NNT=16) was even better than similar estimates in the statin prevention trials ''4S'' and ''WOSCOPS''.
    Low-protein diet in puberty impairs testosterone output and energy metabolism in male rats. de Oliveira Júlio Cezar,de Moura Egberto Gaspar,Miranda Rosiane Aparecida,de Moraes Ana Maria Praxedes,Barella Luiz Felipe,da Conceição Ellen Paula Santos,Gomes Rodrigo Mello,Ribeiro Tatiane Aparecida,Malta Ananda,Martins Isabela Peixoto,Franco Claudinéia Conationi da Silva,Lisboa Patrícia Cristina,Mathias Paulo Cezar de Freitas The Journal of endocrinology We examined the long-term effects of protein restriction during puberty on the function of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in male rats. Male Wistar rats from the age of 30 to 60 days were fed a low-protein diet (4%, LP). A normal-protein diet (20.5%) was reintroduced to rats from the age of 60 to 120 days. Control rats were fed a normal-protein diet throughout life (NP). Rats of 60 or 120 days old were killed. Food consumption, body weight, visceral fat deposits, lipid profile, glycemia, insulinemia, corticosteronemia, adrenocorticotropic hormone (ACTH), testosteronemia and leptinemia were evaluated. Glucose-insulin homeostasis, pancreatic-islet insulinotropic response, testosterone production and hypothalamic protein expression of the androgen receptor (AR), glucocorticoid receptor (GR) and leptin signaling pathway were also determined. LP rats were hypophagic, leaner, hypoglycemic, hypoinsulinemic and hypoleptinemic at the age of 60 days ( < 0.05). These rats exhibited hyperactivity of the HPA axis, hypoactivity of the HPG axis and a weak insulinotropic response ( < 0.01). LP rats at the age of 120 days were hyperphagic and exhibited higher visceral fat accumulation, hyperleptinemia and dyslipidemia; lower blood ACTH, testosterone and testosterone release; and reduced hypothalamic expression of AR, GR and SOCS3, with a higher pSTAT3/STAT3 ratio ( < 0.05). Glucose-insulin homeostasis was disrupted and associated with hyperglycemia, hyperinsulinemia and increased insulinotropic response of the pancreatic islets. The cholinergic and glucose pancreatic-islet responses were small in 60-day-old LP rats but increased in 120-day-old LP rats. The hyperactivity of the HPA axis and the suppression of the HPG axis caused by protein restriction at puberty contributed to energy and metabolic disorders as long-term consequences. 10.1530/JOE-17-0606
    Antihypertensive effects of flutamide in rats that are exposed to a low-protein diet in utero. Gangula Pandu R R,Reed Luckey,Yallampalli Chandrasekhar American journal of obstetrics and gynecology OBJECTIVE:We investigated whether gestational age of in utero low-protein diet played a role in the subsequent development of adult hypertension and whether it is gender dependent and examined whether flutamide (a specific, nonsteroidal competitive antagonist of the androgen receptor) reduces blood pressure in rat offspring that are exposed to in utero low-protein diet (6%). STUDY DESIGN:Pregnant rats were fed either with 20% protein (control) or 6% protein (low-protein diet) from day 1 or day 12 of gestation. Fetoplacental weights and mortality rates of pups were assessed. Systolic blood pressure, mean arterial blood pressure, and circulatory hormone levels in offspring were determined. In addition, male and female hypertensive offspring were treated with flutamide, and their blood pressure was monitored. RESULTS:After delivery, pup weights were reduced, and pup mortality rates increased in the low-protein diet-day 1 group. Systolic blood pressure and mean arterial blood pressure were elevated in low-protein diet-day 1 males and females and low-protein diet-day 2 males. Significant (P < .05) reduction in blood pressure was achieved with flutamide in low-protein diet-day 1 females. Serum estradiol levels were decreased (P < .05) in low-protein diet-day 1 females; flutamide attenuated this effect. CONCLUSION:The day of in utero insult by low-protein diet is critical in the induction of adult hypertension; the severity is gender dependent. Flutamide was found to protect against hypertension only in females. 10.1016/j.ajog.2004.09.008
    Maternal low-protein diet in female rat heart: possible protective effect of estradiol. Braz G R F,Emiliano A S,Sousa S M,Pedroza A A S,Santana D F,Fernandes M P,da Silva A I,Lagranha C J Journal of developmental origins of health and disease Several studies have shown that maternal low-protein (LP) diet induces detrimental effects in cardiovascular system and oxidative stress in male animals. Additional studies suggested that female has lower incidence of cardiovascular disease. However until present data, the possible effects of estradiol on the undernutrition during gestational and lactation periods are not discussed. The present study was conducted to evaluate the effects of a maternal LP diet during gestational and lactation period on oxidative balance in the female rat hearts ventricles at two ages. Dams were fed with normal protein (NP) or a LP diet during the gestational and lactation period, and their female offspring were divided into age groups (22 or 122 days, corresponding to a low or high estrogen level) composing four experimental groups. Evaluating the nutritional effect showed an increase in oxidative stress biomarkers and decrease in enzymatic defense in LP-22D compared with NP-22D. In contrast, no changes were observed in malondialdehyde and carbonyls, but an increase in glutathione-S-transferase (GST) activity in the LP-122D compared with NP-122D. The global oxy-score in the LP-22D group indicated a predominance of oxidative damage when compared with NP-22D, while in LP-122D group the global oxy-score was restored to NP-122D levels. Evaluating the estradiol effect, our data show a significant decrease in oxidative stress with increase in CAT and GST activity, associated with increase in intracellular thiols. Our data suggest that in situation with low levels of estradiol, hypoproteic diet during gestation and lactation period has detrimental effects on heart, however when estradiol levels raise, the detrimental effects induced are mitigated. 10.1017/S2040174417000058
    Effect of dietary protein levels on sex hormones in growing male rats kept under constant darkness. Hanai Miho,Esashi Takatoshi Experimental animals The purpose of this experiment was to clarify the effects of dietary protein levels on the gonadal development and sex hormones in male rats kept under constant darkness as a model of disturbed daily rhythm. Four-week-old male rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle). Two kinds of experimental diet were prepared, one with low dietary protein levels (9% casein) and one with normal levels (18% casein). Harper mineral mixture and Panvitan were used as mineral and vitamin sources, respectively. After 4 weeks, gonadal weight, serum testosterone, and other hormone contents were evaluated. The gonadal weight in the constant darkness groups (D-groups) was lower than that in the normal lighting groups (N-groups). Although the low-protein diet in the D-groups significantly reduced gonadal weight, the normal-protein diet mitigated the reduction of gonadal weight in rats kept under constant darkness. Serum testosterone and androstenedione concentrations were lower in D-group rats fed the low-protein diet. There were no effects of lighting condition or protein levels on serum luteinizing hormone (LH), follicle- stimulating hormone (FSH), or progesterone concentrations. These results indicate that the suppression of gonadal development in D-group rats fed the low-protein diet was caused by low testosterone, which we attribute to the inhibition of synthesized androstenedione, a precursor of testosterone. The present study showed that constant darkness and the low- protein diet inhibited the synthetic pathway from progesterone to androstenedione. 10.1538/expanim.61.555