共0篇 平均IF=NaN (-) 更多分析

    加载中

    logo
    Antiadipogenic effect of dietary apigenin through activation of AMPK in 3T3-L1 cells. Ono Mafuyu,Fujimori Ko Journal of agricultural and food chemistry Adipocyte differentiation (adipogenesis) is a complex process including the coordinated changes in hormone sensitivity and gene expression in response to various stimuli. Natural compounds are known to be involved in the regulation of this process. Here we investigated the effects of dietary apigenin, a plant flavonoid, on adipogenesis. Apigenin suppressed adipocyte differentiation of mouse adipocytic 3T3-L1 cells and reduced the accumulation of intracellular lipids. Quantitative PCR and Western blot analyses revealed that apigenin decreased the levels of peroxisome proliferator-activated receptor γ and its target genes such as fatty acid binding protein 4 (aP2) and stearoyl-CoA desaturase. Apigenin decreased or had no effect on the expression of lipolytic genes such as adipose triglyceride lipase, hormone sensitive lipase, and monoacyl glyceride lipase, thereby reducing glycerol release from adipocytes. Noteworthily, apigenin activated 5'-adenosine monophosphate-activated protein kinase (AMPK) in an apigenin dose-dependent manner, which activation is known to suppress adipogenesis. These results provide a novel insight into the molecular mechanism involved in the action of apigenin: the apigenin-induced activation of AMPK leads to decreased expression of adipogenic and lipolytic genes, thus suppressing adipogenesis in 3T3-L1 cells. Thus, dietary apigenin may contribute to lower body-fat content and body-weight gain through the activation of AMPK. 10.1021/jf203490a
    Apigenin Ameliorates the Obesity-Induced Skeletal Muscle Atrophy by Attenuating Mitochondrial Dysfunction in the Muscle of Obese Mice. Choi Won Hee,Son Hyo Jeong,Jang Young Jin,Ahn Jiyun,Jung Chang Hwa,Ha Tae Youl Molecular nutrition & food research SCOPE:It was investigated whether apigenin (AP) protected against skeletal muscle atrophy induced by obesity. METHODS AND RESULTS:Mice were fed a high-fat diet (HFD) for 9 weeks to induce obesity, and then were assigned to two groups; the HFD group received a high-fat diet, and the HFD+AP group received a 0.1% AP-containing HFD. After additional feeding of the experimental diet for 8 weeks, mice in the HFD group were highly obese compared with the mice in the standard diet fed mice group. The mice in the AP-treated group showed less fat pad accumulation and less inflammatory cytokines without body weight reduction. The weight of skeletal muscle in the AP group tended to increase as compared with that of the HFD group. Furthermore, AP reduced the expression of atrophic genes, including MuRF1 and Atrogin-1, but increased the exercise capacity. The mitochondrial function and mitochondrial biogenesis were enhanced by AP. In cultured C2C12 cells, AP also suppressed palmitic acid-induced muscle atrophy and mitochondrial dysfunction. In addition, AP activated AMP-activated protein kinase (AMPK) in the C2C12 and the muscle of HFD-induced obese mice. CONCLUSION:The results suggested that AP ameliorated the obesity-induced skeletal muscle atrophy by attenuating mitochondrial dysfunction. 10.1002/mnfr.201700218
    Apigenin and luteolin display differential hypocholesterolemic mechanisms in mice fed a high-fat diet. Wong Tsz Yan,Tan Yan Qin,Lin Shu-Mei,Leung Lai K Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Hypercholesterolemia is a major risk factor in the development of atherosclerosis. High blood cholesterol can be the result of increased biosynthesis or reduced elimination of cholesterol in the system. Increased consumption of fruits and vegetables is recommended for patients suffering from hypercholesterolemia. The plant food flavones apigenin and luteolin have previously been shown to suppress the synthesis of cholesterol in human hepatocytes. The effectiveness of these two flavones in controlling blood cholesterol was examined in a mouse model in the present study. Mice were fed a high-fat diet and apigenin or luteolin at 50 and 250 ppm was mixed in the diet. After 8 weeks of treatment, the administration of 250 ppm apigenin or 250 ppm luteolin could modulate the total and serum non-HDL cholesterol. The expressions of srebf-2 mRNA, Srebp-2 protein and Hmgcr protein were decreased in the livers of apigenin-treated mice; meanwhile, AMPK was activated in this group of mice. In contrast, suppressed ncp1l1 and induced abcg-5/8 mRNA expressions were seen in the intestinal mucosa of luteolin-fed animals. Increased fecal cholesterol content was also observed in the luteolin-treated mice. These results revealed that apigenin suppressed the biosynthesis of cholesterol, whereas luteolin promoted the elimination of cholesterol. In summary, this study illustrated that the two flavones could attenuate high-fat feeding-induced hypercholesterolemia in two different mechanisms. 10.1016/j.biopha.2017.11.131
    The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity. Gentile Daniela,Fornai Matteo,Colucci Rocchina,Pellegrini Carolina,Tirotta Erika,Benvenuti Laura,Segnani Cristina,Ippolito Chiara,Duranti Emiliano,Virdis Agostino,Carpi Sara,Nieri Paola,Németh Zoltán H,Pistelli Laura,Bernardini Nunzia,Blandizzi Corrado,Antonioli Luca PloS one BACKGROUND AND PURPOSE:Apigenin can exert beneficial actions in the prevention of obesity. However, its putative action on obesity-associated bowel motor dysfunctions is unknown. This study examined the effects of apigenin on colonic inflammatory and motor abnormalities in a mouse model of diet-induced obesity. EXPERIMENTAL APPROACH:Male C57BL/6J mice were fed with standard diet (SD) or high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day). After 8 weeks, body and epididymal fat weight, as well as cholesterol, triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1β and IL-6 levels, and let-7f expression were also examined. Colonic infiltration by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS and tachykininergic contractions were recorded in vitro from colonic longitudinal muscle preparations. KEY RESULTS:When compared to SD mice, HFD animals displayed increased body weight, epididymal fat weight and metabolic indexes. HFD mice showed increments in colonic MDA, IL-1β and IL-6 levels, as well as a decrease in let-7f expression in both colonic and epididymal tissues. HFD mice displayed an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an increase in SP and iNOS expression in myenteric ganglia of HFD mice. In preparations from HFD mice, electrically evoked contractions upon NOS blockade or mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin counteracted the increase in body and epididymal fat weight, as well as the alterations of metabolic indexes. Apigenin reduced also MDA, IL-1β and IL-6 colonic levels as well as eosinophil infiltration, SP and iNOS expression, along with a normalization of electrically evoked tachykininergic and nitrergic contractions. In addition, apigenin normalized let-7f expression in epididymal fat tissues, but not in colonic specimens. CONCLUSIONS AND IMPLICATIONS:Apigenin prevents systemic metabolic alterations, counteracts enteric inflammation and normalizes colonic dysmotility associated with obesity. 10.1371/journal.pone.0195502
    Apigenin ameliorates HFD-induced NAFLD through regulation of the XO/NLRP3 pathways. Lv Yanan,Gao Xiaona,Luo Yan,Fan Wentao,Shen Tongtong,Ding Chenchen,Yao Ming,Song Suquan,Yan Liping The Journal of nutritional biochemistry Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver-related morbidity and mortality disease in the world. However, no effective pharmacological treatment for NAFLD has been found. In this study, we used a high fat diet (HFD)-induced NAFLD model to investigate hepatoprotective effect of apigenin (API) against NAFLD and further explored its potential mechanism. Our results demonstrated that gavage administration of API could mitigate HFD-induced liver injury, enhance insulin sensitivity and markedly reduce lipid accumulation in HFD-fed mice livers. In addition, histological analysis showed that hepatic steatosis and macrophages recruitment in the API treatment group were recovered compared with mice fed with HFD alone. Importantly, API could reverse the HFD-induced activation of the NLRP3 inflammasome, further reduced inflammatory cytokines IL-1β and IL-18 release, accompanied with the inhibition of xanthine oxidase (XO) activity and the reduction of uric acid and reactive oxygen species (ROS) production. The pharmacological role of API was further confirmed using free fatty acid (FFA) induced cell NAFLD model. Taking together, our results demonstrated that API could protect against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation. These protective effects may be partially attributed to the regulation of XO by API, which further modulated NLRP3 inflammasome activation and inflammatory cytokines IL-1β and IL-18 release. Therefore API is a potential therapeutic agent for the prevention of NAFLD. 10.1016/j.jnutbio.2019.05.015
    Dietary Apigenin promotes lipid catabolism, thermogenesis, and browning in adipose tissues of HFD-Fed mice. Sun Ya-Sai,Qu Wei Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association Dietary Apigenin (AP), a natural flavonoid from plants, could alleviate high-fat diet (HFD) induced obesity and its complication. Nonetheless, the direct correlation between dietary AP and their effects in adipose tissues remained unclear. In this study, male C57BL/6 mice were fed with low-fat diet, HFD with or without 0.04% (w/w) AP for 12 weeks. Dietary AP ameliorated HFD induced body weight gain, glucose intolerance, and insulin resistance. Energy expenditure was increased with no influence on energy intake, which indicated us that AP prevented obesity by enhancing energy export. Interestingly, AP activated lipolysis (ATGL/FOXO1/SIRT1) without higher cycling free fatty acids (FFAs). FFAs were consumed by the upregulation of fatty acid oxidation (AMPK/ACC), thermogenesis, and browning (UCP-1, PGC-1α). Additionally, adipose tissue metabolic inflammation (NF-кB, MAPK) was also reduced by AP. Our study proposed that dietary AP could be explored as a new dietary strategy to combat obesity and related insulin resistance. 10.1016/j.fct.2019.110780
    Apigenin, flavonoid component isolated from Gentiana veitchiorum flower suppresses the oxidative stress through LDLR-LCAT signaling pathway. Dou Xiaoju,Zhou Ziqi,Ren Ruimei,Xu Mingjin Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Flower of Gentiana veitchiorum has traditionally been used as an herbal medicine in Tibet for treatment of variola, respiratory infection, and pneumonia. However, the effective components contained in flower are not identified yet, and the underlying mechanisms for anti-inflammatory, antibacterial, and antioxidative activities remain to be elucidated. Here, we first extracted the flavonoid mixture from G. veitchiorum flower. The mixture was then further isolated and the within compounds was identified through the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The results showed that apigenin (4',5,7-trihydroxyflavone) was the most abundant flavonoid in G. veitchiorum flower. We next examined the antioxidative activity of the extracted apigenin using the ferric reducing/antioxidant power (FRAP), the 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assays and found that a positive correlation between apigenin concentration and reactive oxygen species (ROS) scavenging rate. The biochemical assays further revealed that the levels of total cholesterol (TC), triglyceride (TG), and malondialdehyde (MDA) were reduced, while the activity of superoxide dismutase (SOD) was increased after apigenin treatment in hyperlipidemic rats. Moreover, we performed histopathological investigations and found that the lipidic deposition patterns were recovered and the amount of lipid vacuoles was significantly reduced in apigenin-treated hyperlipidemic rat liver. Western blotting assay showed that the expression of low-density lipoprotein receptor (LDLR) and lecithin-cholesterol acyltransferase (LCAT) were up-regulated in the apigenin-treated samples. Overall, our results demonstrated that the apigenin isolated from G. veitchiorum flower exhibited radical scavenging activities, and reversed the high fat diet-induced oxidative damage in rats. Its antioxidative activities are probably achieved via LDLR-LCAT signaling pathway. 10.1016/j.biopha.2020.110298
    Diosmetin has therapeutic efficacy in colitis regulating gut microbiota, inflammation, and oxidative stress via the circ-Sirt1/Sirt1 axis. Li Hai-Long,Wei Yi-Ying,Li Xiao-He,Zhang Shan-Shan,Zhang Ruo-Tong,Li Jin-He,Ma Bo-Wei,Shao Shuai-Bo,Lv Zi-Wei,Ruan Hao,Zhou Hong-Gang,Yang Cheng Acta pharmacologica Sinica Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg · d) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg · d) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1β, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification. 10.1038/s41401-021-00726-0
    Lipase Inhibitors for Obesity: A Review. Liu Tian-Tian,Liu Xiao-Tian,Chen Qing-Xi,Shi Yan Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie With the rapid increase in the population of obese individuals, obesity has become a global problem. Many kinds of chronic metabolic diseases easily caused by obesity have received increasing attention from researchers. People are also striving to find various safe and effective treatment methods as well as anti-obesity medicines. Pancreatic lipase (PL) inhibitors have received substantial attention from researchers in recent years, and PL inhibitors from natural products have attracted much attention due to their structural diversity, low toxicity and wide range of sources. They have been used in the intestinal tract, blood, and the central nervous system with no side effects, and these advantages could lead to a new generation of diet pills or health care products with great development potential. This article is mainly aimed at discussing the research of obesity drug treatment with PL inhibitors and offers a brief review of related properties and the use of PL inhibitors in the field of weight loss. 10.1016/j.biopha.2020.110314
    Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice. Lee Juneyoung,d'Aigle John,Atadja Louise,Quaicoe Victoria,Honarpisheh Pedram,Ganesh Bhanu P,Hassan Ahmad,Graf Joerg,Petrosino Joseph,Putluri Nagireddy,Zhu Liang,Durgan David J,Bryan Robert M,McCullough Louise D,Venna Venugopal Reddy Circulation research RATIONALE:The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown. OBJECTIVE:To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy. METHODS AND RESULTS:Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (, , , and ) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. CONCLUSIONS:This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host. 10.1161/CIRCRESAHA.119.316448
    Gut microbiota-derived short-chain fatty acids regulate IL-17 production by mouse and human intestinal γδ T cells. Dupraz Louise,Magniez Aurélie,Rolhion Nathalie,Richard Mathias L,Da Costa Grégory,Touch Sothea,Mayeur Camille,Planchais Julien,Agus Allison,Danne Camille,Michaudel Chloé,Spatz Madeleine,Trottein François,Langella Philippe,Sokol Harry,Michel Marie-Laure Cell reports Gut interleukin-17A (IL-17)-producing γδ T cells are tissue-resident cells that are involved in both host defense and regulation of intestinal inflammation. However, factors that regulate their functions are poorly understood. In this study, we find that the gut microbiota represses IL-17 production by cecal γδ T cells. Treatment with vancomycin, a Gram-positive bacterium-targeting antibiotic, leads to decreased production of short-chain fatty acids (SCFAs) by the gut microbiota. Our data reveal that these microbiota-derived metabolites, particularly propionate, reduce IL-17 and IL-22 production by intestinal γδ T cells. Propionate acts directly on γδ T cells to inhibit their production of IL-17 in a histone deacetylase-dependent manner. Moreover, the production of IL-17 by human IL-17-producing γδ T cells from patients with inflammatory bowel disease (IBD) is regulated by propionate. These data contribute to a better understanding of the mechanisms regulating gut γδ T cell functions and offer therapeutic perspectives of these cells. 10.1016/j.celrep.2021.109332
    Resveratrol inhibits lipid accumulation in the intestine of atherosclerotic mice and macrophages. Ye Guozhu,Chen Guoyou,Gao Han,Lin Yi,Liao Xu,Zhang Han,Liu Xinyu,Chi Yulang,Huang Qiansheng,Zhu Huimin,Fan Yuhua,Dong Sijun Journal of cellular and molecular medicine Disordered intestinal metabolism is highly correlated with atherosclerotic diseases. Resveratrol protects against atherosclerotic diseases. Accordingly, this study aims to discover novel intestinal proatherosclerotic metabolites and potential therapeutic targets related to the anti-atherosclerotic effects of resveratrol. An untargeted metabolomics approach was employed to discover novel intestinal metabolic disturbances during atherosclerosis and resveratrol intervention. We found that multiple intestinal metabolic pathways were significantly disturbed during atherosclerosis and responsive to resveratrol intervention. Notably, resveratrol abolished intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice. Meanwhile, oleate accumulation was one of the most prominent alterations in intestinal metabolism. Moreover, resveratrol attenuated oleate-triggered accumulation of total cholesterol, esterified cholesterol and neutral lipids in mouse RAW 264.7 macrophages by activating ABC transporter A1/G1-mediated cholesterol efflux through PPAR (peroxisome proliferator-activated receptor) α/γ activation. Furthermore, we confirmed that PPARα and PPARγ activation by WY14643 and pioglitazone, respectively, alleviated oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids by accelerating ABC transporter A1/G1-mediated cholesterol efflux. This study provides the first evidence that resveratrol abolishes intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice, and that resveratrol suppresses oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids in macrophages by activating PPARα/γ signalling. 10.1111/jcmm.14323
    Pasteurized increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice. Depommier Clara,Van Hul Matthias,Everard Amandine,Delzenne Nathalie M,De Vos Willem M,Cani Patrice D Gut microbes Accumulating evidence points to as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized . Finally, we observed that treatment with pasteurized increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism. 10.1080/19490976.2020.1737307
    Interactions of dietary fat with the gut microbiota: Evaluation of mechanisms and metabolic consequences. Mokkala Kati,Houttu Noora,Cansev Tuğçe,Laitinen Kirsi Clinical nutrition (Edinburgh, Scotland) The current scientific literature proposes that both the amount and type of dietary fat modulate homeostasis of the gut microbiota; disturbances in homeostasis may have metabolic consequences with potentially serious clinical manifestations. The evidence for interactions between dietary fat and gut microbiota has been mostly derived from animal studies, but there is now also evidence emerging from human studies. We will review the current literature on how dietary fat influences the gut microbiota, particularly focusing on the type of fat. Mechanisms detailing how this crosstalk may impact on host metabolism and health will also be discussed. Some studies have reported somewhat controversial findings and therefore we will evaluate critically which possible aspects should be considered when interpreting current and planning further studies to explore the diet-microbiota crosstalk and its metabolic and clinical implications for the host. 10.1016/j.clnu.2019.05.003
    Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice. Xia Bo,Shi Xiao Chen,Xie Bao Cai,Zhu Meng Qing,Chen Yan,Chu Xin Yi,Cai Guo He,Liu Min,Yang Shi Zhen,Mitchell Grant A,Pang Wei Jun,Wu Jiang Wei PLoS biology Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications. 10.1371/journal.pbio.3000688
    Diosmetin Protects Against Obesity and Metabolic Dysfunctions Through Activation of Adipose Estrogen Receptors in Mice. Xie Baocai,Pan Dengke,Liu Huan,Liu Min,Shi Xiaochen,Chu Xinyi,Lu Junfeng,Zhu Mengqing,Xia Bo,Wu Jiangwei Molecular nutrition & food research SCOPE:Obesity is a major public health and economic problem of global significance. Here, we investigate the role of diosmetin, a natural flavonoid presents mainly in citrus fruits, in the regulation of obesity and metabolic dysfunctions in mice. METHODS AND RESULTS:Eight-week-old male C57BL/6 mice fed a high-fat diet (HFD) or 5-week-old male ob/ob mice fed a normal diet are treated with diosmetin (50 mg kg daily) or vehicle for 8 weeks. Diosmetin treatment decreases body weight and fat mass, improves glucose tolerance and insulin resistance in obese mice. These metabolic benefits are mainly attributed to increase energy expenditure via enhancing thermogenesis in brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Mechanistically, diosmetin acts as an agonist for estrogen receptors (ERs), and subsequently elevates adipose expressions of ERs in mice and in cultured adipocytes. When ERs are blocked by their antagonist fulvestrant in mice, diosmetin loses its beneficial effects, suggesting that ERs are indispensable for the metabolic benefits of diosmetin. CONCLUSION:The results indicate that diosmetin may be a potential anti-obesity nutritional supplement and could be explored for low ERs-related obesity populations. 10.1002/mnfr.202100070
    Allicin Improves Metabolism in High-Fat Diet-Induced Obese Mice by Modulating the Gut Microbiota. Shi Xin'e,Zhou Xiaomin,Chu Xinyi,Wang Jie,Xie Baocai,Ge Jing,Guo Yuan,Li Xiao,Yang Gongshe Nutrients Allicin, naturally present in the bulbs of the lily family, has anticancer, blood pressure lowering, blood fat lowering and diabetes improving effects. Recent studies have shown that allicin promotes the browning of white adipocytes and reduces the weight gain of mice induced by high-fat diet. While the gut microbiota has a strong relationship with obesity and energy metabolism, the effect of allicin on weight loss via gut microorganisms is still unclear. In this study, we treated obese mice induced by high-fat diet with allicin to determine its effects on fat deposition, blood metabolic parameters and intestinal morphology. Furthermore, we used high-throughput sequencing on a MiSeq Illumina platform to determine the gut microorganisms' species. We found that allicin significantly reduced the weight gain of obese mice by promoting lipolysis and thermogenesis, as well as blood metabolism and intestinal morphology, and suppressing hepatic lipid synthesis and transport. In addition, allicin changed the composition of the intestinal microbiota and increased the proportion of beneficial bacteria. In conclusion, our study showed that allicin improves metabolism in high-fat induced obese mice by modulating the gut microbiota. Our findings provide a theoretical basis for further elucidation of the weight loss mechanism of allicin. 10.3390/nu11122909
    Effect of Fermented Corn-Soybean Meal on Serum Immunity, the Expression of Genes Related to Gut Immunity, Gut Microbiota, and Bacterial Metabolites in Grower-Finisher Pigs. Lu Junfeng,Zhang Xiaoyu,Liu Yihao,Cao Haigang,Han Qichun,Xie Baocai,Fan Lujie,Li Xiao,Hu Jianhong,Yang Gongshe,Shi Xin'e Frontiers in microbiology Fermented corn-soybean meal (fermented feed, FF) is commonly used in swine production, but the effects of FF on gut health remain unclear. In this study, serum immunity, mRNA abundances of antimicrobial peptides (AMPs) and Toll-like receptors ), bacterial abundance in the duodenum and colon, and colonic metabolic phenotypes were determined in crossbred barrows (Duroc × Landrace × Large White) fed FF or normal feed (unfermented feed, UF) ( = 6). When compared to the UF group, the results showed that serum levels of IgG and IgM were significantly increased in FF group pigs ( < 0.05). FF significantly decreased the abundances of Bacteroides and Verrucomicrobia in the duodenum and decreased the abundances of Bacteroides, Proteobacteria, and Verrucomicrobia in the colon while it significantly increased the abundances of Firmicutes and Actinobacteria ( < 0.05). Furthermore, a Spearman's correlation analysis showed that serum immunity and the expression of genes related to gut immunity were associated with bacterial strains at the family level. Moreover, differentially abundant colonic microbiota were associated with colonic metabolites. LC-MS data analyses identified a total of 1,351 metabolites that markedly differed between the UF and FF groups. C5-Branched dibasic acid metabolism was significantly upregulated whereas the purine metabolism was significantly downregulated ( < 0.05) in the colonic digesta of pigs in the FF meal group compared to the UF meal group. Collectively, these results indicated that FF meal could influence serum immunity and the expression of genes related to gut immunity, correlating with the gut microbiota and bacterial metabolites in grower-finisher pigs. This study may provide an alternative strategy for improving the intestinal health of grower-finisher pigs. 10.3389/fmicb.2019.02620
    A Potential Nutraceutical Candidate Lactucin Inhibits Adipogenesis through Downregulation of JAK2/STAT3 Signaling Pathway-Mediated Mitotic Clonal Expansion. Wang Xin,Liu Min,Cai Guo He,Chen Yan,Shi Xiao Chen,Zhang Cong Cong,Xia Bo,Xie Bao Cai,Liu Huan,Zhang Rui Xin,Lu Jun Feng,Zhu Meng Qing,Yang Shi Zhen,Chu Xin Yi,Zhang Dan Yang,Wang Yong Liang,Wu Jiang Wei Cells The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 μM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity. 10.3390/cells9020331
    Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production. Chen Yan,Cai Guo He,Xia Bo,Wang Xin,Zhang Cong Cong,Xie Bao Cai,Shi Xiao Chen,Liu Huan,Lu Jun Feng,Zhang Rui Xin,Zhu Meng Qing,Liu Min,Yang Shi Zhen,Yang Zhang Dan,Chu Xin Yi,Khan Rajwali,Wang Yong Liang,Wu Jiang Wei FASEB journal : official publication of the Federation of American Societies for Experimental Biology Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3-L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production. However, when ATP is depleted by rotenone, an inhibitor of the respiratory chain, the promotive role of Aco2 in adipogenesis is abolished. In contrast to Aco2 overexpression, deficiency of Aco2 markedly reduced lipogenesis and adipogenesis, along with the decreased mitochondrial biogenesis and ATP production. Supplementation of isocitrate efficiently rescued the inhibitory effect of Aco2 deficiency. Similarly, the restorative effect of isocitrate was abolished in the presence of rotenone. Together, these results show that Aco2 sustains normal adipogenesis through mediating ATP production, revealing a potential mechanistic link between TCA cycle enzyme and lipid synthesis. Our work suggest that regulation of adipose tissue mitochondria function may be a potential way for combating abnormal adipogenesis related diseases such as obesity and lipodystrophy. 10.1096/fj.201903224RR
    The gut mycobiome of healthy mice is shaped by the environment and correlates with metabolic outcomes in response to diet. Mims Tahliyah S,Abdallah Qusai Al,Stewart Justin D,Watts Sydney P,White Catrina T,Rousselle Thomas V,Gosain Ankush,Bajwa Amandeep,Han Joan C,Willis Kent A,Pierre Joseph F Communications biology As an active interface between the host and their diet, the gut microbiota influences host metabolic adaptation; however, the contributions of fungi have been overlooked. Here, we investigate whether variations in gut mycobiome abundance and composition correlate with key features of host metabolism. We obtained animals from four commercial sources in parallel to test if differing starting mycobiomes can shape host adaptation in response to processed diets. We show that the gut mycobiome of healthy mice is shaped by the environment, including diet, and significantly correlates with metabolic outcomes. We demonstrate that exposure to processed diet leads to persistent differences in fungal communities that significantly associate with differential deposition of body mass in male mice compared to mice fed standardized diet. Fat deposition in the liver, transcriptional adaptation of metabolically active tissues and serum metabolic biomarker levels are linked with alterations in fungal community diversity and composition. Specifically, variation in fungi from the genera Thermomyces and Saccharomyces most strongly associate with metabolic disturbance and weight gain. These data suggest that host-microbe metabolic interactions may be influenced by variability in the mycobiome. This work highlights the potential significance of the gut mycobiome in health and has implications for human and experimental metabolic studies. 10.1038/s42003-021-01820-z
    Extra-Virgin Olive Oil with Natural Phenolic Content Exerts an Anti-Inflammatory Effect in Adipose Tissue and Attenuates the Severity of Atherosclerotic Lesions in Ldlr-/-.Leiden Mice. Luque-Sierra Amparo,Alvarez-Amor Leticia,Kleemann Robert,Martín Franz,Varela Lourdes M Molecular nutrition & food research SCOPE:The present study investigates the effect of olive oils with different phenolic content in high-fat diets (HFDs) on hypertrophy and inflammation in adipose tissue and associated atherosclerosis, in the context of obesity. METHODS AND RESULTS:Ldlr-/-.Leiden mice were fed three different HFDs for 32 weeks and were compared with mice fed the standard low-fat diet (LFD). The different fats provided in the HFDs were lard (HFD-L), extra-virgin olive oil (EVOO; 79 mg kg of phenolic compounds, HFD-EVOO), or EVOO rich in phenolic compounds (OL, 444 mg kg of phenolic compounds, HFD-OL). All HFD-fed mice became obese, but only HFD-L-induced adipocyte hypertrophy. HFD-EVOO mice exhibited the greatest levels of Adiponectin in adipose tissue and presented atherosclerotic lesions similar to the LFD group, with a very low count of monocyte/macrophage compared with HFD-L and HFD-OL mice. Enrichment of the phenolic content of olive oil reduced the secretion of nitrites/nitrates in the aorta, but atherosclerosis was not attenuated in HFD-OL mice compared to other HFD mice. CONCLUSION:Consumption of olive oil with a natural content of phenolic compounds attenuates adipose tissue hypertrophy and inflammation and exerts antiatherosclerotic effects in mice. A higher phenolic content of olive oil did not provide further benefits in the prevention of atherosclerosis. 10.1002/mnfr.201800295
    Dietary fats suppress the peritoneal seeding of colorectal cancer cells through the TLR4/Cxcl10 axis in adipose tissue macrophages. Xiang Wei,Shi Rongchen,Zhang Dapeng,Kang Xia,Zhang Lili,Yuan Jing,Zhang Xuan,Miao Hongming Signal transduction and targeted therapy Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is a terminal phase of malignancy with no effective strategies for the prevention of this condition. Here we established PC models in mice by intraperitoneal engraftment of CRC cells and revealed an unexpected role for a high-fat diet (HFD) in preventing metastatic seeding in the visceral fat. Mechanistically, the HFD stimulated the activation of adipose tissue macrophages (ATMs) toward an M1-like phenotype and enhanced ATM tumor phagocytosis in a TLR4-dependent manner. Furthermore, the TLR4-Cxcl10 axis in ATMs promoted T cell recruitment, and M1-like macrophages stimulated T cell activation in tumor-seeded fats. The inhibitory effect of the HFD on tumor seeding was abolished with the ablation of macrophages, inactivation of T cells, or blockade of the TLR4-Cxcl10 axis in macrophages. Finally, we showed that a HFD and conventional chemotherapeutic agents (oxaliplatin or 5-fluorouracil) synergistically improved the survival of tumor-seeded mice. Collectively, our findings demonstrate that peritoneal seeding of CRC can be suppressed by short-term treatment with a HFD in the early phase, providing a novel concept for the management of these patients in the clinic. 10.1038/s41392-020-00327-z
    Dietary Fats High in Linoleic Acids Impair Antitumor T-cell Responses by Inducing E-FABP-Mediated Mitochondrial Dysfunction. Cancer research The most recent American Dietary Guidelines (2020-2025) recommend shifting dietary fats from solid saturated fats to unsaturated oils. Dietary oils contain different compositions of unsaturated fatty acids (UFA). Oleic acid (OA) and linoleic acid (LA) are the most common UFA in dietary oils. How individual UFA in oils regulate immune cell function and cancer risk remains unclear. Here we demonstrated that high-fat diets (HFD) rich either in OA or LA induced a similar degree of murine obesity, but the LA-rich HFD specifically promoted mammary tumor growth. LA impaired antitumor T-cell responses by promoting naïve T-cell apoptosis and inhibiting TNFα production. While exogenous OA and LA were taken up by T cells with similar efficacy, only LA induced significant mitochondrial reactive oxygen species production and lipid peroxidation. Importantly, naïve T cells predominantly expressed epidermal fatty acid binding protein (E-FABP), which is central in facilitating LA mitochondrial transport and cardiolipin incorporation. Genetic depletion of E-FABP rescued LA-impaired T-cell responses and suppressed LA-rich HFD-associated mammary tumor growth. Collectively, these data suggest that dietary oils high in LA promote mammary tumors by inducing E-FABP-mediated T-cell dysfunction. SIGNIFICANCE: These findings suggest that modulation of dietary oil composition and inhibition of E-FABP activity may represent novel strategies to enhance T-cell function in the prevention and treatment of obesity-associated cancers. 10.1158/0008-5472.CAN-21-0757
    Supplementation with Sodium Butyrate Modulates the Composition of the Gut Microbiota and Ameliorates High-Fat Diet-Induced Obesity in Mice. Fang Wanjun,Xue Hongliang,Chen Xu,Chen Ke,Ling Wenhua The Journal of nutrition BACKGROUND:Short-chain fatty acids (SCFAs) have been reported to ameliorate obesity. However, the underlying mechanisms require further investigation. OBJECTIVE:The aim of this study was to determine the role of butyrate, an SCFA, in the regulation of obesity, low-grade chronic inflammation, and alterations of microbiota composition in mice. METHODS:Male C57BL/6J mice, 4-5 wk of age, were divided into 3 groups (n = 8 mice/group): low-fat diet (LFD; 10% energy from fat), high-fat diet (HFD; 45% energy from fat), or high-fat diet plus sodium butyrate (HSB). HSB mice received sodium butyrate at a concentration of 0.1 M in drinking water for 12 wk. Measures of inflammation, obesity, and intestinal integrity were assessed. Serum lipopolysaccharide (LPS) concentrations were measured in the 3 groups. Fecal samples were collected for gut microbiota analysis. RESULTS:In HFD mice, body weight gain and hepatic triglyceride (TG), serum interleukin-6 (IL-6), and serum tumor necrosis factor (TNF)-α levels were 1-4 times higher than those in LFD mice (P < 0.05); they were 34-42% lower in HSB mice compared with HFD mice (P < 0.05). The HFD group had 28%-48% lower mRNA expression of both Tjp1 and Ocln in the ileum and colon compared with levels in LFD or HSB mice (P < 0.05), whereas there was no difference in expression levels between LFD and HSB mice. Furthermore, in HSB mice, serum LPS concentration was 53% lower compared with that in HFD mice but still 23% higher than that in LFD mice (P < 0.05). Results from principal component analysis showed that HSB and LFD mice had a similar gut microbiota structure, which was significantly different from that in HFD mice (P < 0.05). CONCLUSIONS:Sodium butyrate administration beneficially changed HFD-induced gut microbiota composition and improved intestinal barrier, leading to lower serum LPS concentrations. These changes may correspond with improvements in obesity-related lipid accumulation and low-grade chronic inflammation. 10.1093/jn/nxy324
    Diet, lipids and colon cancer. Choi Songhwa,Snider Ashley J International review of cell and molecular biology Dietary fat is digested and absorbed in the small intestine and can then be utilized as an energy source and/or as a reservoir for other bioactive lipid species. Excessive dietary fat has been implicated in the induction and/or aggravation of several diseases, including colorectal cancer (CRC). Diets with high fat content have been shown to exacerbate CRC through regulation of intestinal inflammation and proliferation, as well as alteration of bile acid pools, microbiota, and bioactive lipid species. This chapter will investigate the effects of dietary fat on CRC development and pathobiology, and possible mechanisms for specific lipid species in those processes. 10.1016/bs.ircmb.2019.07.001
    Emerging roles of metabolites of ω3 and ω6 essential fatty acids in the control of intestinal inflammation. Nagatake Takahiro,Kunisawa Jun International immunology The gastrointestinal tract is continuously exposed to the external environment, which contains numerous non-self antigens, including food materials and commensal micro-organisms. For the maintenance of mucosal homeostasis, the intestinal epithelial layer and mucosal immune system simultaneously provide the first line of defense against pathogens and are tightly regulated to prevent their induction of inflammatory responses to non-pathogenic antigens. Defects in mucosal homeostasis lead to the development of inflammatory and associated intestinal diseases, such as Crohn's disease, ulcerative colitis, food allergy and colorectal cancer. The recent discovery of novel dietary ω3 and ω6 lipid-derived metabolites-such as resolvin, protectin, maresin, 17,18-epoxy-eicosatetraenoic acid and microbe-dependent 10-hydroxy-cis-12-octadecenoic acid-and their potent biologic effects on the regulation of inflammation have initiated a new era of nutritional immunology. In this review, we update our understanding of the role of lipid metabolites in intestinal inflammation. 10.1093/intimm/dxy086
    Gastrointestinal Disorders and Metabolic Syndrome: Dysbiosis as a Key Link and Common Bioactive Dietary Components Useful for their Treatment. De Filippis Anna,Ullah Hammad,Baldi Alessandra,Dacrema Marco,Esposito Cristina,Garzarella Emanuele Ugo,Santarcangelo Cristina,Tantipongpiradet Ariyawan,Daglia Maria International journal of molecular sciences Gastrointestinal (GI) diseases, which include gastrointestinal reflux disease, gastric ulceration, inflammatory bowel disease, and other functional GI disorders, have become prevalent in a large part of the world population. Metabolic syndrome (MS) is cluster of disorders including obesity, hyperglycemia, hyperlipidemia, and hypertension, and is associated with high rate of morbidity and mortality. Gut dysbiosis is one of the contributing factors to the pathogenesis of both GI disorder and MS, and restoration of normal flora can provide a potential protective approach in both these conditions. Bioactive dietary components are known to play a significant role in the maintenance of health and wellness, as they have the potential to modify risk factors for a large number of serious disorders. Different classes of functional dietary components, such as dietary fibers, probiotics, prebiotics, polyunsaturated fatty acids, polyphenols, and spices, possess positive impacts on human health and can be useful as alternative treatments for GI disorders and metabolic dysregulation, as they can modify the risk factors associated with these pathologies. Their regular intake in sufficient amounts also aids in the restoration of normal intestinal flora, resulting in positive regulation of insulin signaling, metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. This review is designed to focus on the health benefits of bioactive dietary components, with the aim of preventing the development or halting the progression of GI disorders and MS through an improvement of the most important risk factors including gut dysbiosis. 10.3390/ijms21144929
    Regulation of Intestinal Inflammation by Dietary Fats. Frontiers in immunology With the epidemic of human obesity, dietary fats have increasingly become a focal point of biomedical research. Epidemiological studies indicate that high-fat diets (HFDs), especially those rich in long-chain saturated fatty acids (e.g., Western Diet, National Health Examination survey; NHANES 'What We Eat in America' report) have multi-organ pro-inflammatory effects. Experimental studies have confirmed some of these disease associations, and have begun to elaborate mechanisms of disease induction. However, many of the observed effects from epidemiological studies appear to be an over-simplification of the mechanistic complexity that depends on dynamic interactions between the host, the particular fatty acid, and the rather personalized genetics and variability of the gut microbiota. Of interest, experimental studies have shown that certain saturated fats (e.g., lauric and myristic fatty acid-rich coconut oil) could exert the opposite effect; that is, desirable anti-inflammatory and protective mechanisms promoting gut health by unanticipated pathways. Owing to the experimental advantages of laboratory animals for the study of mechanisms under well-controlled dietary settings, we focus this review on the current understanding of how dietary fatty acids impact intestinal biology. We center this discussion on studies from mice and rats, with validation in cell culture systems or human studies. We provide a scoping overview of the most studied diseases mechanisms associated with the induction or prevention of Inflammatory Bowel Disease in rodent models relevant to Crohn's Disease and Ulcerative Colitis after feeding either high-fat diet (HFD) or feed containing specific fatty acid or other target dietary molecule. Finally, we provide a general outlook on areas that have been largely or scarcely studied, and assess the effects of HFDs on acute and chronic forms of intestinal inflammation. 10.3389/fimmu.2020.604989
    High fat diet-induced obesity increases the formation of colon polyps induced by azoxymethane in mice. Chen Jiezhong,Huang Xu-Feng Annals of translational medicine BACKGROUND:Obesity has been found to be associated with colon cancer. However, the mechanism of this relationship is unclear and thus a good animal model is required. Our previous research showed that some mice developed diet-induced obesity (DIO) whilst others were diet-resistant (DR) when fed a high-fat diet. METHODS:In the present study, we have tested the effects of a high-fat diet on the formation of colon polyps induced by azoxymethane (AOM) in both DIO and DR mice. RESULTS:We found that the DIO mice have developed 2.5 times of polyps compared to the DR mice (P<0.05) and 3.4 times of polyps compared to the low fat fed mice (P<0.05). Although the DR mice tended to have more polyps than the low-fat diet fed mice, this was not statistically significant. The DIO mice could have an increased polyp formation due to obesity-related cancer risk factors and different gene expression from DR mice. CONCLUSIONS:DIO mice could be used as an appropriate model for studying obesity-associated colon cancer; however DR mice are not suitable because they don't show any significant weight gains to indicate obesity. 10.3978/j.issn.2305-5839.2015.03.46
    Emerging nonmetabolic functions of skin fat. Guerrero-Juarez Christian F,Plikus Maksim V Nature reviews. Endocrinology Although the major white adipose depots evolved primarily to store energy, secrete hormones and thermo-insulate the body, multiple secondary depots developed additional specialized and unconventional functions. Unlike any other fat tissue, dermal white adipose tissue (dWAT) evolved a large repertoire of novel features that are central to skin physiology, which we discuss in this Review. dWAT exists in close proximity to hair follicles, the principal appendages of the skin that periodically grow new hairs. Responding to multiple hair-derived signals, dWAT becomes closely connected to cycling hair follicles and periodically cycles itself. At the onset of new hair growth, hair follicles secrete activators of adipogenesis, while at the end of hair growth, a reduction in the secretion of activators or potentially, an increase in the secretion of inhibitors of adipogenesis, results in fat lipolysis. Hair-driven cycles of dWAT remodelling are uncoupled from size changes in other adipose depots that are controlled instead by systemic metabolic demands. Rich in growth factors, dWAT reciprocally signals to hair follicles, altering the activation state of their stem cells and modulating the pace of hair regrowth. dWAT cells also facilitate skin repair following injury and infection. In response to wounding, adipose progenitors secrete repair-inducing activators, while bacteria-sensing adipocytes produce antimicrobial peptides, thus aiding innate immune responses in the skin. 10.1038/nrendo.2017.162
    Repeal and Replace: Adipocyte Regeneration in Wound Repair. Horsley Valerie,Watt Fiona Cell stem cell Adipocyte precursor cells generate lipid-filled mature adipocytes in multiple tissues during a high-fat diet and in skin during hair follicle growth. In Science, Plikus et al. report that myofibroblasts can generate lipid-filled adipocytes in large skin wounds that regenerate hair follicles, suggesting a new source of adipogenic progenitor cells. 10.1016/j.stem.2017.03.015
    Anatomical, Physiological, and Functional Diversity of Adipose Tissue. Zwick Rachel K,Guerrero-Juarez Christian F,Horsley Valerie,Plikus Maksim V Cell metabolism Adipose tissue depots can exist in close association with other organs, where they assume diverse, often non-traditional functions. In stem cell-rich skin, bone marrow, and mammary glands, adipocytes signal to and modulate organ regeneration and remodeling. Skin adipocytes and their progenitors signal to hair follicles, promoting epithelial stem cell quiescence and activation, respectively. Hair follicles signal back to adipocyte progenitors, inducing their expansion and regeneration, as in skin scars. In mammary glands and heart, adipocytes supply lipids to neighboring cells for nutritional and metabolic functions, respectively. Adipose depots adjacent to skeletal structures function to absorb mechanical shock. Adipose tissue near the surface of skin and intestine senses and responds to bacterial invasion, contributing to the body's innate immune barrier. As the recognition of diverse adipose depot functions increases, novel therapeutic approaches centered on tissue-specific adipocytes are likely to emerge for a range of cancers and regenerative, infectious, and autoimmune disorders. 10.1016/j.cmet.2017.12.002
    Obesity increases inflammation and impairs lymphatic function in a mouse model of lymphedema. Savetsky Ira L,Torrisi Jeremy S,Cuzzone Daniel A,Ghanta Swapna,Albano Nicholas J,Gardenier Jason C,Joseph Walter J,Mehrara Babak J American journal of physiology. Heart and circulatory physiology Although obesity is a major clinical risk factor for lymphedema, the mechanisms that regulate this effect remain unknown. Recent reports have demonstrated that obesity is associated with acquired lymphatic dysfunction. The purpose of this study was to determine how obesity-induced lymphatic dysfunction modulates the pathological effects of lymphatic injury in a mouse model. We used a diet-induced model of obesity in adult male C57BL/6J mice in which experimental animals were fed a high-fat diet and control animals were fed a normal chow diet for 8-10 wk. We then surgically ablated the superficial and deep lymphatics of the midportion of the tail. Six weeks postoperatively, we analyzed changes in lymphatic function, adipose deposition, inflammation, and fibrosis. We also compared responses to acute inflammatory stimuli in obese and lean mice. Compared with lean control mice, obese mice had baseline decreased lymphatic function. Lymphedema in obese mice further impaired lymphatic function and resulted in increased subcutaneous adipose deposition, increased CD45(+) and CD4(+) cell inflammation (P < 0.01), and increased fibrosis, but caused no change in the number of lymphatic vessels. Interestingly, obese mice had a significantly increased acute inflammatory reaction to croton oil application. In conclusion, obese mice have impaired lymphatic function at baseline that is amplified by lymphatic injury. This effect is associated with increased chronic inflammation, fibrosis, and adipose deposition. These findings suggest that obese patients are at higher risk for lymphedema due to impaired baseline lymphatic clearance and an increased propensity for inflammation in response to injury. 10.1152/ajpheart.00244.2014
    Effect of the herbal medicines in obesity and metabolic syndrome: A systematic review and meta-analysis of clinical trials. Payab Moloud,Hasani-Ranjbar Shirin,Shahbal Nazila,Qorbani Mostafa,Aletaha Azadeh,Haghi-Aminjan Hamed,Soltani Akbar,Khatami Fatemeh,Nikfar Shekoufeh,Hassani Shokoufeh,Abdollahi Mohammad,Larijani Bagher Phytotherapy research : PTR Obesity is a medical situation in which excess body fat has gathered because of imbalance between energy intake and energy expenditure. In spite of the fact that the variety of studies are available for obesity treatment and management, its "globesity" still remains a big challenge all over the world. The current systematic review and meta-analysis aimed to evaluate the efficacy, safety, and mechanisms of effective herbal medicines in the management and treatment of obesity and metabolic syndrome in human. We systematically searched all relevant clinical trials via Web of Science, Scopus, PubMed, and the Cochrane database to assess the effects of raw or refined products derived from plants or parts of plants on obesity and metabolic syndrome in overweight and obesity adult subjects. All studies conducted by the end of May 2019 were considered in the systematic review. Data were extracted independently by two experts. The quality assessment was assessed using Consolidated Standards of Reporting Trials checklist. The main outcomes were anthropometric indices and metabolic syndrome components. Pooled effect of herbal medicines on obesity and metabolic syndrome were presented as standardized mean difference (SMD) and 95% confidence interval (CI). A total of 279 relevant clinical trials were included. Herbals containing green tea, Phaseolus vulgaris, Garcinia cambogia, Nigella sativa, puerh tea, Irvingia gabonensis, and Caralluma fimbriata and their active ingredients were found to be effective in the management of obesity and metabolic syndrome. In addition, C. fimbriata, flaxseed, spinach, and fenugreek were able to reduce appetite. Meta-analysis showed that intake of green tea resulted in a significant improvement in weight ([SMD]: -0.75 [-1.18, -0.319]), body mass index ([SMD]: -1.2 [-1.82, -0.57]), waist circumference ([SMD]: -1.71 [-2.66, -0.77]), hip circumference ([SMD]: -0.42 [-1.02, -0.19]), and total cholesterol, ([SMD]: -0.43 [-0.77, -0.09]). In addition, the intake of P. vulgaris and N. sativa resulted in a significant improvement in weight ([SMD]: -0.88, 95 % CI: [-1.13, -0.63]) and triglyceride ([SMD]: -1.67, 95 % CI: [-2.54, -0.79]), respectively. High quality trials are still needed to firmly establish the clinical efficacy of the plants in obesity and metabolic syndrome. 10.1002/ptr.6547
    Pulmonary Circulation in Obesity, Diabetes, and Metabolic Syndrome. Khaing Phue,Pandit Pooja,Awsare Bharat,Summer Ross Comprehensive Physiology Obesity, diabetes mellitus, and the metabolic syndrome are important risk factors for the development of cardiovascular disease, with significant impact on human morbidity and mortality. Several decades of research have accumulated considerable knowledge about the mechanisms by which metabolic conditions precipitate systemic cardiovascular diseases. In short, these mechanisms are thought to involve changes in the external environment of vascular cells, which are mediated by the pro-inflammatory effects of adipokines, free fatty acids, and hyperglycemia. Thus, it has been hypothesized that the pulmonary circulation, witnessing similar insults as the systemic circulation, may be equally vulnerable to the development of vascular disease. Accordingly, recent attention has focused on exploring the mechanistic and epidemiological relationships among obesity, type 2 diabetes mellitus, metabolic syndrome, and pulmonary vascular diseases. In this article, we discuss in detail the preclinical evidence showing a modest but perceivable impact of metabolic disorders on the pulmonary circulation. In addition, we review the existing epidemiological studies examining the relationship among cardiovascular risk factors and pulmonary vascular diseases, using the acute respiratory distress syndrome and pulmonary arterial hypertension as examples. We conclude by discussing areas of limitations in the field and by suggesting future directions for investigation, including the notion that the pulmonary circulation may, in fact, be a resilient entity in the setting of some metabolic perturbations. © 2020 American Physiological Society. Compr Physiol 10:297-316, 2020. 10.1002/cphy.c190018
    Impact of Obesity and Metabolic Syndrome on Immunity. Andersen Catherine J,Murphy Kelsey E,Fernandez Maria Luz Advances in nutrition (Bethesda, Md.) Obesity is associated with metabolic disturbances that cause tissue stress and dysfunction. Obese individuals are at a greater risk for chronic disease and often present with clinical parameters of metabolic syndrome (MetS), insulin resistance, and systemic markers of chronic low-grade inflammation. It has been well established that cells of the immune system play an important role in the pathogenesis of obesity- and MetS-related chronic diseases, as evidenced by leukocyte activation and dysfunction in metabolic tissues such as adipose tissue, liver, pancreas, and the vasculature. However, recent findings have highlighted the substantial impact that obesity and MetS parameters have on immunity and pathogen defense, including the disruption of lymphoid tissue integrity; alterations in leukocyte development, phenotypes, and activity; and the coordination of innate and adaptive immune responses. These changes are associated with an overall negative impact on chronic disease progression, immunity from infection, and vaccine efficacy. This review presents an overview of the impact that obesity and MetS parameters have on immune system function. 10.3945/an.115.010207
    Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation. Pan Yong,Hui Xiaoyan,Hoo Ruby Lai Chong,Ye Dewei,Chan Cyrus Yuk Cheung,Feng Tianshi,Wang Yu,Lam Karen Siu Ling,Xu Aimin The Journal of clinical investigation Persistent, unresolved inflammation in adipose tissue is a major contributor to obesity-associated metabolic complications. However, the molecular links between lipid-overloaded adipocytes and inflammatory immune cells in obese adipose tissues remain elusive. Here we identified adipocyte-secreted microRNA-34a (miR-34a) as a key mediator through its paracrine actions on adipose-resident macrophages. The expression of miR-34a in adipose tissues was progressively increased with the development of dietary obesity. Adipose-selective or adipocyte-specific miR-34a-KO mice were resistant to obesity-induced glucose intolerance, insulin resistance, and systemic inflammation, and this was accompanied by a significant shift in polarization of adipose-resident macrophages from proinflammatory M1 to antiinflammatory M2 phenotype. Mechanistically, mature adipocyte-secreted exosomes transported miR-34a into macrophages, thereby suppressing M2 polarization by repressing the expression of Krüppel-like factor 4 (Klf4). The suppressive effects of miR-34a on M2 polarization and its stimulation of inflammatory responses were reversed by ectopic expression of Klf4 in both bone marrow-derived macrophages and adipose depots of obese mice. Furthermore, increased miR-34a expression in visceral fat of overweight/obese subjects correlated negatively with reduced Klf4 expression, but positively with the parameters of insulin resistance and metabolic inflammation. In summary, miR-34a was a key component of adipocyte-secreted exosomal vesicles that transmitted the signal of nutrient overload to the adipose-resident macrophages for exacerbation of obesity-induced systemic inflammation and metabolic dysregulation. 10.1172/JCI123069
    Mast cells participate in chronic low-grade inflammation within adipose tissue. Żelechowska P,Agier J,Kozłowska E,Brzezińska-Błaszczyk E Obesity reviews : an official journal of the International Association for the Study of Obesity Obesity is reckoned as one of the civilization diseases, posing a considerable global health issue. Evidence points towards a contribution of multitude immune cell populations in obesity pathomechanism and the development of chronic low-grade inflammation in the expanded adipose tissue. Notably, adipose tissue is a reservoir of mast cells which number in individuals with obesity particularly increased. Some of them tend to degranulation what generate secretion of strong pro-inflammatory and regulatory mediators, as well as cytokines/chemokines. Several lines of evidence suggest that mast cells are strictly associated with pro-inflammatory status in adipose tissue by their indirect impact on immune cell attraction and activation. Furthermore, mast cells affect adipose tissue remodelling and fibrosis by adipocyte differentiation, fibroblast proliferation and enhancing extracellular matrix proteins expression. This review will summarize current knowledge on mast cell features and their role in the development of chronic low-grade inflammation within adipose tissue. 10.1111/obr.12670
    Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue. Saxton Sophie N,Clark Ben J,Withers Sarah B,Eringa Etto C,Heagerty Anthony M Physiological reviews Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity. 10.1152/physrev.00034.2018
    Adipokines at the crossroad between obesity and cardiovascular disease. Molica Filippo,Morel Sandrine,Kwak Brenda R,Rohner-Jeanrenaud Françoise,Steffens Sabine Thrombosis and haemostasis Obesity, and especially excessive visceral adipose tissue accumulation, is considered as a low-grade inflammatory state that is responsible for adipocyte dysfunction and associated metabolic disorders. Adipose tissue displays endocrine functions by releasing pro- or anti-inflammatory bioactive molecules named adipokines. An altered expression of these molecules, provoked by obesity or adipocyte dysregulation, contributes to major metabolic diseases such as insulin resistance and type 2 diabetes mellitus that are important risk factors for cardiovascular disease. However, obesity is also characterised by the expansion of perivascular adipose tissue that acts locally via diffusion of adipokines into the vascular wall. Local inflammation within blood vessels induced by adipokines contributes to the onset of endothelial dysfunction, atherosclerosis and thrombosis, but also to vascular remodelling and hypertension. A fast expansion of obesity is expected in the near future, which will rapidly increase the incidence of these cardiovascular diseases. The focus of this review is to summarise the link between metabolic and cardiovascular disease and discuss current treatment approaches, limitations and future perspectives for more targeted therapies. 10.1160/TH14-06-0513
    Obesity. González-Muniesa Pedro,Mártinez-González Miguel-Angel,Hu Frank B,Després Jean-Pierre,Matsuzawa Yuji,Loos Ruth J F,Moreno Luis A,Bray George A,Martinez J Alfredo Nature reviews. Disease primers Excessive fat deposition in obesity has a multifactorial aetiology, but is widely considered the result of disequilibrium between energy intake and expenditure. Despite specific public health policies and individual treatment efforts to combat the obesity epidemic, >2 billion people worldwide are overweight or obese. The central nervous system circuitry, fuel turnover and metabolism as well as adipose tissue homeostasis are important to comprehend excessive weight gain and associated comorbidities. Obesity has a profound impact on quality of life, even in seemingly healthy individuals. Diet, physical activity or exercise and lifestyle changes are the cornerstones of obesity treatment, but medical treatment and bariatric surgery are becoming important. Family history, food environment, cultural preferences, adverse reactions to food, perinatal nutrition, previous or current diseases and physical activity patterns are relevant aspects for the health care professional to consider when treating the individual with obesity. Clinicians and other health care professionals are often ill-equipped to address the important environmental and socioeconomic drivers of the current obesity epidemic. Finally, understanding the epigenetic and genetic factors as well as metabolic pathways that take advantage of 'omics' technologies could play a very relevant part in combating obesity within a precision approach. 10.1038/nrdp.2017.34
    An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression. Qin Yufeng,Roberts John D,Grimm Sara A,Lih Fred B,Deterding Leesa J,Li Ruifang,Chrysovergis Kaliopi,Wade Paul A Genome biology BACKGROUND:The gut microbiome, a key constituent of the colonic environment, has been implicated as an important modulator of human health. The eukaryotic epigenome is postulated to respond to environmental stimuli through alterations in chromatin features and, ultimately, gene expression. How the host mediates epigenomic responses to gut microbiota is an emerging area of interest. Here, we profile the gut microbiome and chromatin characteristics in colon epithelium from mice fed either an obesogenic or control diet, followed by an analysis of the resultant changes in gene expression. RESULTS:The obesogenic diet shapes the microbiome prior to the development of obesity, leading to altered bacterial metabolite production which predisposes the host to obesity. This microbiota-diet interaction leads to changes in histone modification at active enhancers that are enriched for binding sites for signal responsive transcription factors. These alterations of histone methylation and acetylation are associated with signaling pathways integral to the development of colon cancer. The transplantation of obesogenic diet-conditioned microbiota into germ free mice, combined with an obesogenic diet, recapitulates the features of the long-term diet regimen. The diet/microbiome-dependent changes are reflected in both the composition of the recipient animals' microbiome as well as in the set of transcription factor motifs identified at diet-influenced enhancers. CONCLUSIONS:These findings suggest that the gut microbiome, under specific dietary exposures, stimulates a reprogramming of the enhancer landscape in the colon, with downstream effects on transcription factors. These chromatin changes may be associated with those seen during colon cancer development. 10.1186/s13059-018-1389-1
    Effects of Curcumin in a Mouse Model of Very High Fat Diet-Induced Obesity. Koboziev Iurii,Scoggin Shane,Gong Xiaoxia,Mirzaei Parvin,Zabet-Moghaddam Masoud,Yosofvand Mohammad,Moussa Hanna,Jones-Hall Yava,Moustaid-Moussa Naima Biomolecules Worldwide rates of Western-diet-induced obesity epidemics are growing dramatically. Being linked with numerous comorbidities and complications, including cardiovascular disease, type 2 diabetes, cancer, chronic inflammation, and osteoarthritis (OA), obesity represents one of the most threatening challenges for modern healthcare. Mouse models are an invaluable tool for investigating the effects of diets and their bioactive components against high fat diet (HFD)-induced obesity and its comorbidities. During recent years, very high fat diets (VHFDs), providing 58-60% kcal fat, have become a popular alternative to more traditional HFDs, providing 40-45% total kcal fat, due to the faster induction of obesity and stronger metabolic responses. This project aims to investigate if the 60% fat VHFD is suitable to evaluate the protective effects of curcumin in diet-induced obesity and osteoarthritis. B6 male mice, prone to diet-induced metabolic dysfunction, were supplemented with VHFD without or with curcumin for 13 weeks. Under these experimental conditions, feeding mice a VHFD for 13 weeks did not result in expected robust manifestations of the targeted pathophysiologic conditions. Supplementing the diet with curcumin, in turn, protected the animals against obesity without significant changes in white adipocyte size, glucose clearance, and knee cartilage integrity. Additional research is needed to optimize diet composition, curcumin dosage, and duration of dietary interventions to establish the VHFD-induced obesity for evaluating the effects of curcumin on metabolic dysfunctions related to obesity and osteoarthritis. 10.3390/biom10101368
    Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice. Hussain Ahtesham,Cho Jin Sook,Kim Jong-Seok,Lee Young Ik Molecules (Basel, Switzerland) BACKGROUND:Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). OBJECTIVE:The aim of this study to evaluate the effects of polyphenol enriched herbal complex (/ellagic acid, Bunge/vitexin, chlorogenic acid, /cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. METHODS:Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group's liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. RESULTS:Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). CONCLUSIONS:The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model. 10.3390/molecules26020302
    Danning tablets alleviate high fat diet-induced obesity and fatty liver in mice via modulating SREBP pathway. Ma Yujie,Li Jinmei,Ju Zhengcai,Huang Wendong,Wang Zhengtao,Yang Li,Ding Lili Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:The traditional Chinese formula Danning tablets exhibit wide clinical applications in liver and gallbladder diseases, and currently it is reported to be effective on fatty liver disease in clinical trials. However, the underlying mechanisms remain elusive. AIM OF THE STUDY:The purpose of the present study was to assess the effects and potential pharmacological mechanisms of Danning tablet against high fat diet (HFD)-induced obesity, fatty liver, and related metabolic disorders in mice. MATERIALS AND METHODS:C57BL/6 J male mice were treated with HFD for 12 weeks to trigger obesity and fatty liver condition. Then those mice were randomly divided into 5 groups, namely HFD, Danning tablet (0.75, 1.5 or 3 g/kg bodyweight) or lovastatin (30 mg/kg bodyweight) for extra 6 weeks' treatment of HFD. Food intake and bodyweight were recorded each week. In the last week, before the mice were sacrificed, fasting blood glucose levels and insulin levels were measured. Furthermore, insulin and glucose tolerance tests were performed. Blood and hepatic lipid levels were examined, the lipid metabolism-associated gene expressions and protein levels in the liver or adipose tissues were assayed after sacrificing all mice. RESULTS:Our results demonstrated that a high dose of Danning tablet (3 g/kg) treatment mitigated body weight gain, reduced blood and hepatic cholesterol and triglyceride levels. The morphology analysis showed that Danning tablets could reduce lipid accumulation in both liver and brown adipose tissue. Moreover, Danning tablets could improve fasting blood glucose levels and ameliorate glucose and insulin tolerance in HFD-induced obese mice. Furthermore, qRT-PCR analysis revealed that the mRNA expressions of SREBP-1 and SREBP-2 as well as their target genes were remarkedly down-regulated in the liver and adipose tissue of diet-induced obesity (DIO) mice after treating those mice with Danning tablets. CONCLUSION:Our results indicated that Danning tablets could improve the obesity-induced metabolic associated fatty liver disease (MAFLD) and related metabolic disorders. The potential mechanism may probably involve the regulation of the SREBP pathway. 10.1016/j.jep.2021.114320
    High-fat feeding disrupts daily eating behavior rhythms in obesity-prone but not in obesity-resistant male inbred mouse strains. American journal of physiology. Regulatory, integrative and comparative physiology Abnormal meal timing, like skipping breakfast and late-night snacking, is associated with obesity in humans. Disruption of daily eating rhythms also contributes to obesity in mice. When fed a high-fat diet, male C57BL/6J mice have disrupted eating behavior rhythms and they become obese. In contrast to obesity-prone C57BL/6J mice, some inbred strains of mice are resistant to high-fat diet-induced obesity. In this study, we sought to determine whether there are distinct effects of high-fat feeding on daily eating behavior rhythms in obesity-prone and obesity-resistant male mice. Male obesity-prone (C57BL/6J and 129X1/SvJ) and obesity-resistant (SWR/J and BALB/cJ) mice were fed low-fat diet or high-fat diet for 6 wk. Consistent with previous studies, obesity-prone male mice gained more weight and adiposity during high-fat diet feeding than obesity-resistant male mice. The amplitude of the daily rhythm of eating behavior was markedly attenuated in male obesity-prone mice fed high-fat diet, but not in obesity-resistant males. In contrast, high-fat feeding did not differentially affect locomotor activity rhythms in obesity-prone and obesity-resistant male mice. Together, these data suggest that regulation of the daily rhythm of eating may underlie the propensity to develop diet-induced obesity in male mice. 10.1152/ajpregu.00150.2020
    Porcine Acellular Dermal Matrix Increases Fat Survival Rate after Fat Grafting in Nude Mice. Zhu Meishu,Zhu Meihui,Wu Xiaoling,Xu Meiquan,Fan Kunwu,Wang Jinming,Zhang Liyong,Yin Meifang,Wu Jun,Zhu Zhixiang,Yang Guang Aesthetic plastic surgery BACKGROUND:Autologous fat grafts have been widely in use for reconstruction, contour abnormalities, and cosmetic surgeries. However, the grafted fat one-year survival rate is unpredictable and always low (20%-80%). Standardizing the existing transplantation technology is difficult due to the limiting conditions. Scaffold materials or drugs are unsuitable to employ because of legal restrictions, complex production, and undetermined hazards. Therefore, a simpler and more effective approach to improve grafted fat survival rate is using commercial products as additives. Earlier studies proved that porcine acellular dermal matrix (PADM), a biomaterial clinically used for wound repair, could work as a scaffold for lipo-implantation. This study aimed at investigating the hitherto unclear effect of PADM on transplanted fat survival. METHODS:Thirty-two 8-week-old female nude mice were divided into two groups. Control mice received a 300 μl fat injection, while the PADM group mice were injected with a 300 μl PADM-fat mixture. After a 4-week treatment, fat weight and liquefaction ratio were assessed. Histological changes were quantified via hematoxylin & eosin (H&E) staining. Macrophage infiltration and vascular regeneration were revealed using an anti-CD34 antibody. Mouse and human mRNA expression levels were gauged via RNA-sequencing. On the third day post implantation, the mRNA expression levels of inflammatory genes Mcp-1 and Tnf-α were measured by qRT-PCR. RESULTS:The weight of surviving grafted fat did not differ between the control and the PADM group. However, adding PADM significantly decreased fat liquefaction. H&E-stained sections showed that PADM decreased fat necrosis, increased fat tissue regeneration, and raised CD34 levels in the regenerated tissue. RNA-sequencing showed that, compared to controls, fats from PADM-added group expressed more mouse-related mRNA but less human-related mRNA. The following GO and KEGG analysis showed that added PADM increased extracellular matrix (ECM) genes expression levels. The qRT-PCR showed that adding PADM increased Mcp-1 and Tnf-α mRNA expression levels. CONCLUSIONS:In summary, PADM addition increased fat survival rate by reducing fat liquefaction through an increased macrophage infiltration, ECM regeneration, and revascularization. Therefore, PADM addition is a workable application in autologous fat grafting. NO LEVEL ASSIGNED:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . 10.1007/s00266-021-02299-z