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The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study. Leber B,Tripolt N J,Blattl D,Eder M,Wascher T C,Pieber T R,Stauber R,Sourij H,Oettl K,Stadlbauer V European journal of clinical nutrition BACKGROUND/OBJECTIVES:Obesity and metabolic disorders are linked to inflammation via gut microbiota and/or gut permeability. Gut-derived endotoxin triggers inflammation leading to metabolic syndrome (MetS) and contributing to oxidative stress. We intended to investigate the effect of Lactobacillus casei Shirota on gut permeability, presence of endotoxin and neutrophil function in MetS. SUBJECTS/METHODS:Patients with MetS were randomized to receive 3 × 6.5 × 10⁹ CFU L. casei Shirota (probiotic group) or not for 3 months. Gut permeability was assessed by a differential sugar absorption method and by determination of diaminooxidase serum levels, endotoxin by an adapted limulus amoebocyte lysate assay, neutrophil function and toll-like receptor (TLR) expression by flow cytometry and ELISA was used to detect lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) levels. RESULTS:Twenty-eight patients and 10 healthy controls were included. Gut permeability was significantly increased in MetS compared with controls but did not differ between patient groups. None of the patients were positive for endotoxin. LBP and sCD14 levels were not significantly different from healthy controls. High-sensitive C-reactive protein and LBP levels slightly but significantly increased after 3 months within the probiotics group. Neutrophil function and TLR expression did not differ from healthy controls or within the patient groups. CONCLUSIONS:Gut permeability of MetS patients was increased significantly compared with healthy controls. L. casei Shirota administration in the MetS patients did not have any influence on any parameter tested possibly due to too-short study duration or underdosing of L. casei Shirota. 10.1038/ejcn.2012.103
Inhibition of inflammation may enhance nitric oxide availability in patients undergoing bariatric surgery for weight loss. Blum A,Ginat-Maimon L,Yehuda H,Geron N,Ben Ami M,Tamir S Journal of internal medicine BACKGROUND:Weight loss surgery is the most effective treatment for morbid obesity. The mechanisms underlying the beneficial cardiovascular effects are poorly understood, although inhibition of inflammatory markers has been demonstrated. We hypothesized that anti-inflammatory and antioxidative stress reactions are responsible for the beneficial effects of bariatric surgery that have been shown in clinical trials. METHODS:The inflammatory system was studied by measuring mRNA levels of E-selectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and in a cell line (HUVEC-CS) of human umbilical vein endothelial cells that were incubated for 4 h with pools of serum, collected before and 3 months after surgery, from 20 women who underwent bariatric surgery for weight loss. The oxidative stress pathway was examined by mRNA expression of NADPH oxidase (P22(phox) ), paraoxonase (PON2), superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx) and catalase following incubation of the cells for 4 h with serum pools. The nitric oxide (NO) pathway was studied by measuring mRNA levels of inducible NOS and endothelial NOS and by determining nitrite and nitrate levels. To study the functional behaviour of endothelial cells under stress, primary human umbilical vein endothelial cells (PECs) were incubated with the serum pools for 48 h, with lipopolysaccharide (LPS) for the last 4 h. RESULTS:The inflammatory system: incubation of HUVEC-CS cells with serum from women who underwent bariatric surgery led to a significant decrease in mRNA expression of E-selectin and IL-6 postsurgery. Stimulation of PECs with LPS in the presence of serum from women who underwent bariatric surgery caused a more significant difference in E-selectin and TNF-α mRNA expression before and after surgery. The antioxidant system: incubation of HUVEC-CS cells with serum from women who underwent bariatric surgery did not lead to any difference in mRNA expression of P22(phox) , PON2, SOD2, GPx or catalase. Stimulation of PECs with LPS showed that obese women had higher levels of P22(phox) , PON2 and the antioxidant enzymes SOD2, GPx and catalase before and after surgery, compared to the control group. The NO pathway: HUVEC-CS cells incubated with serum from women who underwent bariatric surgery secreted higher nitrite/nitrate levels compared to presurgery serum (P = 0.04). CONCLUSIONS:Inhibition of inflammation and enhanced availability of NO 3 months after bariatric surgery could partly explain the beneficial effects of surgery for weight loss. 10.1111/joim.12379
Endotoxemia, nutrition, and cardiometabolic disorders. Kallio K A Elisa,Hätönen Katja A,Lehto Markku,Salomaa Veikko,Männistö Satu,Pussinen Pirkko J Acta diabetologica AIMS:Circulating lipopolysaccharides (LPSs), associated with both infection and inflammation, may arise from the gastrointestinal tract microbiota, and the levels may be affected by daily nutrition. We investigated whether nutrient intake affects the association of serum LPS activity with prevalent obesity, metabolic syndrome (MetS), diabetes, and coronary heart disease (CHD) and with the risk of incident CHD events. METHODS:The nutrition cohort (n = 2,452, mean age ± SD, 52.2 ± 10.1 years) of the FINRISK 1997 Study was followed up for 10 years. Information on macronutrient intake at baseline was collected from 24-h dietary recall. Serum endotoxin activities were determined by the Limulus amebocyte lysate assay. RESULTS:LPS activity was associated directly with the total energy intake and indirectly with carbohydrate intake in lean, healthy subjects. High LPS was significantly associated with prevalent obesity, MetS, diabetes, and CHD events, independently of established risk factors, CRP, and total energy or nutrient intake. The ORs (95 % CI) were 1.49 (1.21-1.85, p < 0.001, Q2-4 vs. Q1) for obesity, 2.56 (1.97-3.32, p < 0.001, Q2-4 vs. Q1) for MetS, 1.94 (1.06-3.52, p = 0.031, Q2-4 vs. Q1) for CHD, and 1.01 (1.00-1.01, p = 0.032, LPS unit) for diabetes. In the follow-up, high LPS was significantly associated with the risk of CHD events with a hazard ratio of 1.88 (1.13-3.12, p = 0.013, Q2-4 vs. Q1). This association was independent of baseline established risk factors, diet, obesity, MetS, and diabetes. CONCLUSION:A high serum LPS activity is strongly associated with cardiometabolic disorders, which supports the role of bacterial infections and immune response in their etiology. 10.1007/s00592-014-0662-3
Endotoxins are associated with visceral fat mass in type 1 diabetes. Lassenius Mariann I,Ahola Aila J,Harjutsalo Valma,Forsblom Carol,Groop Per-Henrik,Lehto Markku Scientific reports Bacterial lipopolysaccharides (LPS), potent inducers of inflammation, have been associated with chronic metabolic disturbances. Obesity is linked to dyslipidemia, increased body adiposity, and endotoxemia. We investigated the cross-sectional relationships between serum LPS activity and body adiposity as well as inflammation in 242 subjects with type 1 diabetes. Body fat distribution was measured by DXA and serum LPS activity by the limulus amebocyte lysate end-point assay. Since no interaction between visceral fat mass and sex was observed, data were pooled for the subsequent analyses. LPS was independently associated with visceral fat mass, when adjusted for traditional risk factors (age, sex, kidney status, hsCRP, insulin sensitivity). In the multivariate analysis, serum LPS activity and triglyceride concentrations had a joint effect on visceral fat mass, independent of these factors alone. A combination of high LPS and high hsCRP concentrations was also observed in those with the largest visceral fat mass. In conclusion, high serum LPS activity levels were associated with visceral fat mass in subjects with type 1 diabetes strengthening its role in the development of central obesity, inflammation and insulin resistance. 10.1038/srep38887
Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans. Friebe D,Neef M,Kratzsch J,Erbs S,Dittrich K,Garten A,Petzold-Quinque S,Blüher S,Reinehr T,Stumvoll M,Blüher M,Kiess W,Körner A Diabetologia AIMS/HYPOTHESIS:Nicotinamide phosphoribosyltransferase (NAMPT) is a multifunctional protein potentially involved in obesity and glucose metabolism. We systematically studied the association between circulating NAMPT, obesity, interventions and glucose metabolism and investigated potential underlying inflammatory mechanisms. METHODS:Fasting morning NAMPT serum levels were measured in cohorts of lean vs obese children, cohorts of intervention by lifestyle, exercise and bariatric surgery, and during an OGTT. In addition, mRNA expression, protein production and enzymatic activity of NAMPT were assessed from isolated leucocytes and subpopulations. RESULTS:Circulating NAMPT was significantly elevated in obese compared with lean children and declined after obesity interventions concomitantly with the decline in BMI, high-sensitivity C-reactive protein (hsCrP) and leucocyte counts. Circulating NAMPT significantly correlated with glucose metabolism and cardiovascular variables in univariate analyses, but only the association with glucose response during an OGTT was independent from BMI. We therefore assessed the NAMPT dynamic following an oral glucose load and found a significant decline of NAMPT levels to 77.0 ± 0.1% as a function of time, and insulin-to-glucose ratio during an OGTT in obese insulin-resistant adolescents. Circulating NAMPT was, however, most strongly associated with leucocyte counts (r = 0.46, p < 0.001). The leucocyte count itself determined significantly and independently from BMI insulin resistance in multiple regression analyses. We systematically evaluated NAMPT expression among several tissues and found that NAMPT was predominantly expressed in leucocytes. In subsequent analyses of leucocyte subpopulations, we identified higher NAMPT protein concentrations in lysates of granulocytes and monocytes compared with lymphocytes, whereas granulocytes secreted highest amounts of NAMPT protein into cell culture supernatant fractions. We confirmed nicotinamide mononucleotide enzymatic activity of NAMPT in all lysates and supernatant fractions. In monocytes, NAMPT release was significantly stimulated by lipopolysaccharide (LPS) exposure. CONCLUSIONS:Leucocytes are a major source of enzymatically active NAMPT, which may serve as a biomarker or even mediator linking obesity, inflammation and insulin resistance. 10.1007/s00125-010-2042-z
The Effects of Probiotic Supplements on Blood Markers of Endotoxin and Lipid Peroxidation in Patients Undergoing Gastric Bypass Surgery; a Randomized, Double-Blind, Placebo-Controlled, Clinical Trial with 13 Months Follow-Up. Obesity surgery BACKGROUND:The effect of probiotic supplements among subjects undergoing bariatric surgery indicates conflicting results. Moreover, whether these effects remain after ceasing the treatment remained to be elucidated. This study was conducted to assess the effect of probiotic supplements on blood markers of endotoxin (lipopolysaccharides-binding protein: LBP), inflammation and lipid peroxidation (malondialdehyde: MDA) in patients with morbid obesity undergoing the one-anastomosis gastric bypass (OAGB). METHODS:This study is a placebo-controlled, double-blind, and randomized clinical trial and 9 months of additional follow-up. Forty-six morbid obese patients undergoing OAGB were randomized to 4 months of probiotic or placebo supplements. Anthropometric indices and blood concentration of LBP, inflammatory markers, MDA, vitamin D3, and B were measured at 0, 4, and 13 months of study. RESULTS:Probiotic supplements could improve serum LBP (P = 0.039), TNF-α (P = 0.005), vitamin B (P = 0.03), vitamin D3 (P = 0.001), and weight loss (P = 0.01) at month 4 in comparison to placebo; however, only serum MDA concentrations decreased significantly in the probiotic group compared with those in the placebo group (P = 0.013) at the end of follow-up period. DISCUSSION:It was observed that 4 months probiotic supplementation compared with placebo prohibited an elevation in the LBP levels and improved serum TNF-α and 25-OH vitamin D3 concentrations and weight loss in patients undergoing the OAGB surgery. However, these effects did not persist 9 months after the cessation of the treatment. Further investigations are required to find how long supplementation and which dosage of it can benefit body status for the long-term. TRIAL REGISTRATION:This study has been registered at Clinicaltrial.gov with registration number NCT02708589 . 10.1007/s11695-018-03667-6
Prebiotics Reduce Body Fat and Alter Intestinal Microbiota in Children Who Are Overweight or With Obesity. Nicolucci Alissa C,Hume Megan P,Martínez Inés,Mayengbam Shyamchand,Walter Jens,Reimer Raylene A Gastroenterology BACKGROUND & AIMS:It might be possible to manipulate the intestinal microbiota with prebiotics or other agents to prevent or treat obesity. However, little is known about the ability of prebiotics to specifically modify gut microbiota in children with overweight/obesity or reduce body weight. We performed a randomized controlled trial to study the effects of prebiotics on body composition, markers of inflammation, bile acids in fecal samples, and composition of the intestinal microbiota in children with overweight or obesity. METHODS:We performed a single-center, double-blind, placebo-controlled trial of 2 separate cohorts (March 2014 and August 2014) at the University of Calgary in Canada. Participants included children, 7-12 years old, with overweight or obesity (>85th percentile of body mass index) but otherwise healthy. Participants were randomly assigned to groups given either oligofructose-enriched inulin (OI; 8 g/day; n=22) or maltodextrin placebo (isocaloric dose, controls; n=20) once daily for 16 weeks. Fat mass and lean mass were measured using dual-energy-x-ray absorptiometry. Height, weight, and waist circumference were measured at baseline and every 4 weeks thereafter. Blood samples were collected at baseline and 16 weeks, and analyzed for lipids, cytokines, lipopolysaccharide, and insulin. Fecal samples were collected at baseline and 16 weeks; bile acids were profiled using high-performance liquid chromatography and the composition of the microbiota was analyzed by 16S rRNA sequencing and quantitative polymerase chain reaction. The primary outcome was change in percent body fat from baseline to 16 weeks. RESULTS:After 16 weeks, children who consumed OI had significant decreases in body weight z-score (decrease of 3.1%), percent body fat (decrease of 2.4%), and percent trunk fat (decrease of 3.8%) compared with children given placebo (increase of 0.5%, increase of 0.05%, and decrease of 0.3%, respectively). Children who consumed OI also had a significant reduction in level of interleukin 6 from baseline (decrease of 15%) compared with the placebo group (increase of 25%). There was a significant decrease in serum triglycerides (decrease of 19%) in the OI group. Quantitative polymerase chain reaction showed a significant increase in Bifidobacterium spp. in the OI group compared with controls. 16S rRNA sequencing revealed significant increases in species of the genus Bifidobacterium and decreases in Bacteroides vulgatus within the group who consumed OI. In fecal samples, levels of primary bile acids increased in the placebo group but not in the OI group over the 16-week study period. CONCLUSIONS:In a placebo-controlled, randomized trial, we found a prebiotic (OI) to selectively alter the intestinal microbiota and significantly reduce body weight z-score, percent body fat, percent trunk fat, and serum level of interleukin 6 in children with overweight or obesity (Clinicaltrials.gov no: NCT02125955). 10.1053/j.gastro.2017.05.055
Lipopolysaccharide-binding protein is associated with arterial stiffness in patients with type 2 diabetes: a cross-sectional study. Sakura Takeshi,Morioka Tomoaki,Shioi Atsushi,Kakutani Yoshinori,Miki Yuya,Yamazaki Yuko,Motoyama Koka,Mori Katsuhito,Fukumoto Shinya,Shoji Tetsuo,Emoto Masanori,Inaba Masaaki Cardiovascular diabetology BACKGROUND:Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS. Recent evidence indicates the association of circulating LBP levels with obesity, diabetes, and cardiovascular diseases. In this study, we aimed to investigate the relationship between serum LBP levels and arterial stiffness in patients with type 2 diabetes. METHODS:A total of 196 patients with type 2 diabetes, including 101 men and 95 women, were enrolled in this cross-sectional study. Fasting serum LBP levels were determined by enzyme-linked immunosorbent assay. Arterial stiffness was assessed by measuring the aortic pulse wave velocity (PWV). RESULTS:The mean values of serum LBP and aortic PWV were 18.2 μg/mL and 1194 cm/s, respectively. Serum LBP levels were positively correlated with body mass index, triglycerides, high-sensitivity C-reactive protein, and insulin resistance index and were negatively correlated with high-density lipoprotein cholesterol. They were, however, not significantly correlated with aortic PWV in univariate analyses. Multivariate analysis revealed that serum LBP levels were independently and positively associated with aortic PWV (β = 0.135, p = 0.026) after adjusting for age, sex, body mass index, albumin, high-sensitivity C-reactive protein, and other cardiovascular risk factors. Further analyses revealed that the impact of serum LBP levels on aortic PWV was modified by sex, and the association between serum LBP levels and aortic PWV was found to be significant only in men. CONCLUSIONS:Serum LBP levels are associated with arterial stiffness, independent of obesity and traditional cardiovascular risk factors, especially in men with type 2 diabetes. This study indicates a potential role of the LPS/LBP-induced innate immunity in the development and progression of arterial stiffness in type 2 diabetes. 10.1186/s12933-017-0545-3
Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Dewulf Evelyne M,Cani Patrice D,Claus Sandrine P,Fuentes Susana,Puylaert Philippe G B,Neyrinck Audrey M,Bindels Laure B,de Vos Willem M,Gibson Glenn R,Thissen Jean-Paul,Delzenne Nathalie M Gut OBJECTIVE:To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese women. METHODS:A double blind, placebo controlled, intervention study was performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose 50/50 mix; n=15) or placebo (maltodextrin; n=15) for 3 months (16 g/day). Blood, faeces and urine sampling, oral glucose tolerance test, homeostasis model assessment and impedancemetry were performed before and after treatment. The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA. Plasma and urine metabolic profiles were analysed by 1H-NMR spectroscopy. RESULTS:Treatment with ITF prebiotics, but not the placebo, led to an increase in Bifidobacterium and Faecalibacterium prausnitzii; both bacteria negatively correlated with serum lipopolysaccharide levels. ITF prebiotics also decreased Bacteroides intestinalis, Bacteroides vulgatus and Propionibacterium, an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels. No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses. However, ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and/or diabetes. CONCLUSIONS:ITF prebiotics selectively changed the gut microbiota composition in obese women, leading to modest changes in host metabolism, as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures. 10.1136/gutjnl-2012-303304
Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Creely S J,McTernan P G,Kusminski C M,Fisher ff M,Da Silva N F,Khanolkar M,Evans M,Harte A L,Kumar S American journal of physiology. Endocrinology and metabolism UNLABELLED:Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-kappaB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold (P<0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-alpha and IL-6 secretion (IL-6, CONTROL: 2.7+/-0.5 vs. LPS: 4.8+/-0.3 ng/ml; P<0.001; TNF-alpha, CONTROL:1.0+/-0.83 vs. LPS: 32.8+/-6.23 pg/ml; P<0.001). NF-kappaB inhibitor reduced IL-6 in AbdSc adipocytes ( CONTROL:2.7+/-0.5 vs. NF-kappaB inhibitor: 2.1+/-0.4 ng/ml; P<0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-kappaB was increased in T2DM patients (P<0.05), and TLR-2, TRAF-6, and NF-kappaB were increased in LPS-treated adipocytes (P<0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls (r=0.678, P<0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P=0.0395) and serum LPS (reduced by 35%, P=0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM. 10.1152/ajpendo.00302.2006
Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients. Clemente-Postigo M,Queipo-Ortuño M I,Murri M,Boto-Ordoñez M,Perez-Martinez P,Andres-Lacueva C,Cardona F,Tinahones F J Journal of lipid research The low-grade inflammation observed in obesity has been associated with a high-fat diet, though this relation is not fully understood. Bacterial endotoxin, produced by gut microbiota, may be the linking factor. However, this has not been confirmed in obese patients. To study the relationship between a high-fat diet and bacterial endotoxin, we analyzed postprandial endotoxemia in morbidly obese patients after a fat overload. The endotoxin levels were determined in serum and the chylomicron fraction at baseline and 3 h after a fat overload in 40 morbidly obese patients and their levels related with the degree of insulin resistance and postprandial hypertriglyceridemia. The morbidly obese patients with the highest postprandial hypertriglyceridemia showed a significant increase in lipopolysaccharide (LPS) levels in serum and the chylomicron fraction after the fat overload. Postprandial chylomicron LPS levels correlated positively with the difference between postprandial triglycerides and baseline triglycerides. There were no significant correlations between C-reactive protein (CRP) and LPS levels. The main variables contributing to serum LPS levels after fat overload were baseline and postprandial triglyceride levels but not glucose or insulin resistance. Additionally, superoxide dismutase activity decreased significantly after the fat overload. Postprandial LPS increase after a fat overload is related to postprandial hypertriglyceridemia but not to degree of insulin resistance in morbidly obese patients. 10.1194/jlr.P020909
Bariatric surgery decreased the serum level of an endotoxin-associated marker: lipopolysaccharide-binding protein. Yang Po-Jen,Lee Wei-Jei,Tseng Ping-Huei,Lee Po-Huang,Lin Ming-Tsan,Yang Wei-Shiung Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery BACKGROUND:Recent studies have shown serum lipopolysaccharide binding protein (LBP) is associated with obesity and related metabolic disorder. Bariatric surgery can significantly reduce weight, but reports about the change of LBP after bariatric surgery are limited. We investigated LBP concentration and its associations with clinical variables. METHODS:We enrolled 178 obese patients receiving different bariatric surgeries and 38 normal weight individuals. Fasting blood samples were collected at baseline in all and 1 year after surgery in obese individuals. The serum LBP concentration was measured. RESULTS:The percentage of excess weight loss of mini-gastric bypass, Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric band were 72.0±20.0%, 65.5±23.0%, 67.2±18.4%, and 16.1±14.3%, respectively. Serum LBP levels were higher in the obese participants than in the normal weight participants (49.9±15.7 versus 25.2±7.5 μg/mL; P<.001) at baseline and significantly decreased to 35.1±22.6 μg/mL after bariatric surgery (P<.001) in the obese group. In the bariatric participants, after multivariate analyses, preoperative LBP and the change of LBP with surgery were independently associated only with high sensitive C-reactive protein (hs-CRP) (P<.001) and the change of hs-CRP (P = .012), respectively, while none of the postoperative variables was independently associated with LBP. CONCLUSION:LBP is associated with body mass index and hs-CRP. Bariatric surgery significantly decreased the serum level of LBP. The relationship between LBP and hs-CRP disappeared after bariatric surgery. 10.1016/j.soard.2014.02.022
One-year weight management lowers lipopolysaccharide-binding protein and its implication in metainflammation and liver fibrosis. Nien Hsiao-Ching,Sheu Jin-Chuan,Chi Yu-Chiao,Chen Chi-Ling,Kao Jia-Horng,Yang Wei-Shiung PloS one BACKGROUND:Studies showed that the endotoxemia-related biomarker, lipopolysaccharide-binding protein (LBP), is associated with obesity and fatty liver. The level of LBP is reduced after surgical weight loss. This study aimed to verify the change of serum LBP levels after one-year medical weight management in subjects with obesity. METHODS AND FINDINGS:A total of 62 subjects with obesity, 39 subjects with overweight, and 21 subjects with normal body mass index were enrolled for a one-year weight management program. Basic information, body composition analysis, clinical data, serum LBP level, and abdominal ultrasonography findings were collected. At baseline, the serum LBP levels of the obese and overweight subjects were significantly higher than that of the normal group (30.9±7.4 and 29.6±6.3 versus 23.1±5.6 μg/mL, respectively, p<0.001). Serum LBP in subjects with obesity was significantly reduced to 26.5±7.1 μg/mL (p-value < 0.001) after one year. In the multivariate analyses, LBP was associated with high sensitive C-reactive protein (hs-CRP) and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) before weight management in the obese group. Moreover, the change of LBP in response to weight management was significantly related to the changes of hs-CRP, leukocyte count and NFS by multivariate linear regression analysis also in the obese group. CONCLUSION:The serum level of the endotoxemia-related biomarker, LBP, decreases after one-year weight management in the obese subjects. In addition to serving as a metainflammatroy biomarker like hs-CRP, LBP may also be a potential biomarker as a non-invasive biomarker for the evaluation of liver fibrosis in NAFLD. 10.1371/journal.pone.0207882
Association of endotoxaemia with serum free fatty acids in metabolically healthy and unhealthy abdominally obese individuals: a case-control study in northwest of Iran. Saghafi-Asl Maryam,Amiri Parichehr,Naghizadeh Mahsa,Ghavami Seyed Mostafa,Karamzad Nahid BMJ open OBJECTIVES:This study aimed to compare serum free fatty acids (FFAs) and lipopolysaccharide-binding protein (LBP) between metabolically healthy abdominally obese (MHAO) and metabolically unhealthy abdominally obese (MUAO) individuals. We also examined the association between serum FFAs and LBP in the participants. METHODS:In this age-matched and gender-matched case-control study, 164 abdominally obese subjects were recruited from June to November 2015 in the northwest of Iran. Demographic data, dietary intake, body composition, anthropometric indices and physical activity (PA) were assessed. Basal blood samples were collected to determine serum metabolic parameters, FFAs and LBP. Abdominal obesity was defined as having waist circumference ≥95 cm. Those with three or more metabolic alterations were defined as MUAO and those having two or less were classified as MHAO. Data were analysed using SPSS V.17.0. RESULTS:There were no significant differences in dietary intake, anthropometric indices, body composition and PA between the two groups. The odds of MUAO significantly increased by increments in serum fasting blood sugar (OR 3.79, 95% CI 2.25 to 6.40), triglycerides (OR 1.10, 95% CI 1.05 to 1.15), systolic blood pressure (OR 1.02, 95% CI 1.00 to 1.04) and diastolic blood pressure (OR 1.03, 95% CI 1.01 to 1.06) and decreased by increase in serum high-density lipoprotein cholesterol (OR 0.32, 95% CI 0.20 to 0.52). The levels of LBP and FFAs showed no significant differences between the two groups. However, significant correlations were found between LBP and FFAs in pooled population (r=0.712; p<0.001) as well as in cases (r=0.717; p<0.001) and controls (r=0.704; p<0.001). Neither FFAs nor LBP were significantly correlated with dietary intake or metabolic parameters (p>0.05). CONCLUSION:The results indicated that serum LBP and FFAs are highly correlated both in MHAO and MUAO states. In addition, the levels of LBP and FFAs seem to be more related to abdominal obesity than to the presence or absence of metabolic health. 10.1136/bmjopen-2017-015910
Diet influences levels of plasma lipopolysaccharide (LPS) and its soluble receptor (sCD14) in Saudis. Bahijri Suhad Maatoug,Ajabnoor Ghada Mohammad,Hegazy Gehan Abdel-Fattah,Borai Anwar Abdullah,Eldakhakhny Basmah Medhat,Alsheikh Lubna Nihad,Harakeh Steve Mustapha JPMA. The Journal of the Pakistan Medical Association Objective:This study aimed to investigate the association between serum levels of LPS, sCD14 and hs-CRP, and markers of obesity, and dietary composition of healthy adults residing in Jeddah, Saudi Arabia. METHODS:Apparently healthy adults, aged 18-55 years, were recruited from Jeddah population in a cross-sectional design. Anthropometric measurements, and vital signs were taken using standardized techniques. Serum glucose, cholesterol (TC), triglycerides (TG), high-density lipoprotein- cholesterol (HDL-C), hs-CPR, LPS and sCD14 were assayed, and LDL- cholesterol (LDL-C), and atherogenic index of plasma (AIP) were calculated. Means of estimated variables were compared using t-test or Mann-Whitney U-test for two groups and ANOVA for multiple groups. Chi-square, and Pearson's correlation coefficient were used to identify association and correlations between studied variables. RESULTS:Means of TG, LDL-C, and hs-CRP increased significantly in both genders with increasing BMI (p= 0.019, and 0.040 for TG, 0.049, and 0.002 for LDL-C in males and females respectively, and <0.001 for hs-CRP for both). Mean hs-CRP was significantly higher in subjects with abdominal obesity (p=0.025 for men, and 0.001 for women), identified to have metabolic syndrome (p<0.001). Mean sCD14 was significantly elevated in females consuming high quantity of bread (p= 0.033) or drinking tea (p = 0.018). LPS correlated positively with sCD14 in men (p=0.049). CONCLUSIONS:An association between dietary composition and development of bacterial endotoxaemia was found. However, no association between measures of endotoxaemia and increased adiposity and inflammation was found. 10.5455/JPMA.28279
Inflammatory Potential of Diet: Association With Chemerin, Omentin, Lipopolysaccharide-Binding Protein, and Insulin Resistance in the Apparently Healthy Obese. Mirmajidi Susan,Izadi Azimeh,Saghafi-Asl Maryam,Vahid Farhad,Karamzad Nahid,Amiri Parichehr,Shivappa Nitin,Hébert James R Journal of the American College of Nutrition OBJECTIVE:Low-grade inflammation is a characteristic of various conditions, including obesity. Diet is regarded as a strong modifier of inflammation. The potential links between inflammatory properties of diet and adipokines as well as insulin resistance (IR) warrant further investigation. Therefore, this study aimed to examine the associations of the dietary inflammatory index (DII) with serum chemerin, omentin, and lipopolysaccharide-binding protein (LBP) as well as IR among apparently healthy obese adults. DESIGN:In this cross-sectional study, 171 abdominally obese subjects were recruited in the northwest of Iran. Demographic data, dietary intake, anthropometric indices, and physical activity (PA) were assessed. DII scores were calculated based on dietary intake, using a validated 168-item food frequency questionnaire (FFQ). Basal blood samples were collected to determine the biochemical parameters. A linear regression test with adjusted beta estimates was applied for data analysis. RESULT:Compared to those with higher DII score, the group with lower DII score (anti-inflammatory diet) had higher protein (83.62 ± 36.42 g vs. 71.61 ± 25.94 g) and lower carbohydrate (325.00 ± 125.76 g vs. 378.19 ± 137.69 g) intake. Participants with higher DII score had lower consumption of polyunsaturated and monounsaturated fats as well as fiber and higher saturated fats (p < .001). Those with elevated DII score had higher levels of chemerin (p = .034) and LBP (p = .040), compared to those with lower DII. Omentin showed no significant differences between groups with different DII scores. Additionally, people with a more proinflammatory diet had higher FBS (p = .005); however, other markers of IR did not differ by DII scores. CONCLUSIONS:The results suggest that increased inflammatory potential of diet, as indicated by higher DII score, is associated with elevated levels of chemerin and LBP. While DII was positively associated with FBS, no significant correlation was found for insulin and other indices of IR. 10.1080/07315724.2018.1504348
Gut Microbiota and Metabolic Endotoxemia in Young Obese Mexican Subjects. Radilla-Vázquez Romina Belén,Parra-Rojas Isela,Martínez-Hernández Norma Edith,Márquez-Sandoval Yolanda Fabiola,Illades-Aguiar Berenice,Castro-Alarcón Natividad Obesity facts BACKGROUND:The gut microbiota plays an important role in human metabolism; previous studies suggest that the imbalance can cause a metabolic endotoxemia that may be linked to weight gain and insulin resistance. The purpose of this study was to investigate the relationship between the gut microbiota composition, the lipopolysaccharide levels and the metabolic profile in obese and normal-weight young subjects. METHODS:We studied 32 obese (BMI ≥ 30 kg/m2) and 32 normal-weight subjects (BMI = 18.5-24.9 kg/m2), aged 18-25 years. Quantification of intestinal bacteria was performed by real-time PCR. Endotoxin units were determined with the test QCL-1000, and biochemical profile was performed under a standard protocol of Spinreact. RESULTS:Obese individuals had a BMI of 34.5 (32.9-36.45) kg/m2, increased triglycerides (123 vs. 70 mg/dl), total cholesterol (168 vs. 142 mg/dl), and LDL-cholesterol (114 vs. 96.5 mg/dl). In obese subjects body temperature was higher than in normal-weight subjects. We found a greater number of Clostridum leptum and Lactobacillus (p < 0.001) and lower numbers of Prevotella and Escherichia coli (p < 0.001) in the obese group. A decrease of E. coli was associated with an increased risk of lipopolysaccharide levels ranging from 1 to 1.3 EU/ml. A positive correlation was found between serum lipopolysaccharides and BMI (r = 0.46, p = 0.008), triglyceride levels (r = 0.44, p = 0.011) as well as waist circumference (r = 0.34, p = 0.040), being more evident in young obese females. CONCLUSION:Subclinical metabolic endotoxemia determined by serum concentration of lipopolysaccharides was related to the smallest amount of E. coli, high triglyceride levels, and central adiposity in obese young persons. 10.1159/000442479
Exercise reduced pentraxin 3 levels produced by endotoxin-stimulated human peripheral blood mononuclear cells in obese individuals. Slusher Aaron L,Shibata Yoshimi,Whitehurst Michael,Maharaj Arun,Quiles Justin M,Huang Chun-Jung Experimental biology and medicine (Maywood, N.J.) The purpose of this study was to determine whether obesity would reduce the capacity of peripheral blood mononuclear cells (PBMCs) to produce the anti-inflammatory protein pentraxin 3 (PTX3) in response to ex vivo stimulation with lipopolysaccharide (LPS), and if acute aerobic exercise would enhance this PTX3 production capacity. In addition, the inter-relationships of LPS-induced PTX3 with the inflammatory cytokines (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha) were examined. Twenty-one healthy subjects (10 obese and 11 normal-weight) performed an acute bout of aerobic exercise at 75% VO. The capacity of PBMCs to produce PTX3 ex vivo following LPS stimulation was the same in obese and normal-weight subjects at rest, and decreased equally in both subject groups following acute aerobic exercise. This is in contrast to plasma PTX3, which is lower in obese subjects at rest and increased equally in both obese and normal-weight subjects following exercise. In addition, ex vivo PTX3 production was positively associated with IL-6 and IL-10 in response to acute aerobic exercise ( r = 0.686, P = 0.020; r = 0.744, P = 0.009, respectively) in normal-weight, but not in obese individuals ( r = 0.429, P = 0.249; r = 0.453, P = 0.189, respectively). These findings indicate that concentrations of PTX3 observed in plasma are relatively independent of those produced by PBMCs ex vivo and the mechanisms associated with PTX3-mediated anti-inflammatory signaling may differ during obesity. Impact statement Our laboratory has previously demonstrated that obese individuals present with lower plasma concentrations of the anti-inflammatory protein pentraxin 3 (PTX3), whereas acute aerobic exercise increases plasma PTX3 levels similarly compared to normal-weight individuals. As a follow-up, the present study demonstrates that PBMCs isolated from obese and normal-weight individuals produce comparable amounts of PTX3 ex vivo in response to lipopolysaccharide (LPS). Furthermore, given that acute aerobic exercise reduced the ex vivo production of PTX3 in both groups, our results clearly indicate that plasma PTX3 levels are relatively independent of those produced by PBMCs ex vivo. In addition, our findings suggest that the mechanisms associated with PTX3-mediated production of the anti-inflammatory cytokine interleukin 10 may be impaired in obese individuals, and thus provides a key finding necessary for the elucidation of PTX3's role in the mediation of anti-inflammatory profiles and the subsequent amelioration of inflammatory disease during obesity. 10.1177/1535370217706963
Novel associations of serum adropin and lipopolysaccharide-binding protein versus lipid profiles in childhood obesity. Yuan Xin,Chen Ruimin,Ouyang Qian,Lin Xiangquan,Ai Zhuanzhuan,Zhang Ying,Yang Xiaohong Journal of pediatric endocrinology & metabolism : JPEM Background The relationship between cytokines and lipid metabolism has garnered attention given their potential metabolic interaction. However, the relationship between adropin and lipopolysaccharide-binding protein (LBP) and obesity-related inflammation has not been reported, as well as their relationship with serum lipid profiles. Objective This study analyzed the association of serum adropin, leptin, LBP levels and lipid profiles in obese children ranging from 5 to 14 years old. Methods Plasma lipid measurements included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) by standard methods, and serum adropin, leptin and LBP levels was measured by enzyme-linked immunosorbent assay (ELISA). Results One hundred and twenty-four children (9.25 ± 1.59 years) with obesity and 42 controls (8.81 ± 1.94 years) were assessed. Compared with the control group, the serum adropin concentrations in the obesity group were significantly lower, whereas the serum leptin and LBP levels were significantly higher. Pearson's correlation analysis showed that serum adropin levels negatively correlated with TG, waist to hip ratio (WHR) and body mass index (BMI), and positively correlated with HDL-c. Serum LBP levels positively correlated with LDL-c and WHR. After adjusting for LBP, the correlation coefficients of adropin with TG, HDL-c and leptin were more robust. Also, after adjusting for serum LBP, the correlation coefficient of leptin with TG was attenuated, yet remained statistically significant, and the correlation coefficient of leptin with HDL-c was enhanced. Conclusions Children with obesity have decreased serum adropin levels and elevated leptin and LBP levels. Each of the three serum cytokines were associated with lipid metabolism, and this association warrants further study. 10.1515/jpem-2019-0329
Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk. Archives of endocrinology and metabolism OBJECTIVE:Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. SUBJECTS AND METHODS:On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. RESULTS:The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p < 0.01)), insulin (p = 0.02) and triglyceride levels (p = 0.01), lower insulin resistance (homeostasis model assessment - insulin resistance (HOMA-IR) (p = 0.01), triglycerides/glucose (TYG index) (p = 0.02), neck circumference (p = 0.02), risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r -0.46, p = 0.04), neck circumference (r -0.51, p = 0.02), free fat mass (r -0.49, p = 0.02), triglycerides (r -0.43, p = 0.05) and risk of developing T2DM (r -0.61, p = 0.04) were observed. CONCLUSIONS:These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance. 10.1590/2359-3997000000305
Lipopolysaccharide and inflammatory cytokines levels decreased after sleeve gastrectomy in Chinese adults with obesity. Li Ying,Guan Wei,Ma Shuai,Lin Shibo,Yang Ningli,Liu Ruiping,Liang Hui,Zhou Hongwen Endocrine journal Obesity is linked to a low-grade systemic inflammation and lipopolysaccharide (LPS) is a key factor. Sleeve gastrectomy (SG) can significantly cause weight loss, but few reports have looked into the changes of LPS and inflammatory cytokines after surgery. To explore the potential short-term impact of SG on LPS and inflammatory cytokines and their relationship to early metabolic changes in obesity. 30 Chinese adults with obesity (BMI 39.37 ± 8.22 kg/m, 25 female) receiving SG were included in this study. Fasting blood samples were collected at baseline and 30 days after SG. Serum LPS markedly reduced from 336.50 (73.54, 500) pg/mL to 5.00 (5.00, 5.24) pg/mL at 1 month after SG (p < 0.05). There was a significant decrease in plasma IL-6, IL-8, and serum CRP after SG (all p < 0.05). Insulin resistance improved remarkably after surgery as displayed by reductions in fasting insulin level (FINS, p < 0.001), and HOMA-IR (p < 0.001). In addition, visceral fat area (VFA) decreased from 209.70 ± 39.96 cm to 193.28 ± 43.68 cm after SG (p < 0.001). LPS was positively correlated with FINS (r = 0.391, p = 0.033) and HOMA-IR (r = 0.38, p = 0.038) before SG. Meanwhile, VFA was positively associated with CRP (r = 0.388, p = 0.034) before surgery. When assessing 30-days postoperative changes, a positive correlation was found between the variations of LPS, IL-8 and the reduction of VFA. After multivariate analyses, only the reduced IL-8 level was independently associated with the reduction of VFA (p = 0.015). In conclusion, SG can significantly relieve the inflammation in obesity in the short term and LPS might be an earlier predictor of inflammatory changes after surgery. 10.1507/endocrj.EJ18-0446
Toll-like receptor signaling and serum levels of interferon β and lipopolysaccharide binding protein are related to abdominal obesity: a case-control study between metabolically healthy and metabolically unhealthy obese individuals. Naghizadeh Mahsa,Baradaran Behzad,Saghafi-Asl Maryam,Amiri Parichehr,Shanehbandi Dariush,Karamzad Nahid,Mohamed-Khosroshahi Leila Nutrition research (New York, N.Y.) It is still unclear whether toll-like receptor (TLR) signaling and serum levels of inflammatory markers in metabolically unhealthy abdominally obese (MUAO) are due to their obesity and/or their metabolic state. We hypothesized that abdominal obesity is an important mediator of the association of metabolic state with TLR signaling and serum inflammatory markers. Therefore, in this case-control study, we compared the expression levels of TLR4 and Toll/interleukin-1 receptor domain containing adaptor protein-inducing interferon β (TRIF) and serum concentrations of interferon β and lipoprotein-binding protein (LBP) in metabolically healthy abdominally obese (MHAO) and MUAO individuals. Basal blood samples from 65 abdominally obese subjects with waist circumference (WC) of at least 95 cm were collected to determine serum metabolic parameters, IFNβ, and LBP. Those with 3 or more metabolic alterations were defined as MUAO (n = 34), and those having 2 or less were classified as MHAO (n = 31). Furthermore, messenger RNA (mRNA) was isolated from peripheral blood mononuclear cells. TLR4 and TRIF gene expression assay was performed using quantitative real-time polymerase chain reaction. There were significant differences in serum fasting blood sugar (P = .017), triglyceride (P < .001), cholesterol (P = .002), and low-density lipoprotein cholesterol (P = .034) between the MUAO and MHAO groups, whereas no significant difference was observed in the expression ratio of TLR4 and TRIF mRNA and serum levels of IFNβ and LBP. However, a significant correlation was noticed between mRNA expression levels of TLR4 and TRIF (r = 0.50, P < .001) and serum IFNβ and LBP (r = 0.70, P < .001). It is concluded that the expression levels of TLR4 and TRIF as well as serum IFNβ and LBP are more related to abdominal obesity than to metabolic health. 10.1016/j.nutres.2018.03.014