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Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.

ABSTRACT: Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including Ephedra sinica (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via oral gavage over three weeks. High-fat-diet (HFD)-induced obese rats transplanted with EsM lost significant body weight, epididymal fat, and perirenal fat weight, but no remarkable changes were observed in abdominal fat, liver, cecum weight and food efficiency ratio. In addition, treatment with EsM also significantly lowered the fasting blood glucose, serum insulin level, and insulin resistance index. Meanwhile, EsM transplantation significantly reduced gene expression of proinflammatory cytokines interleukin-1 and monocyte chemotactic protein-1. Rats treated with EsM also showed changed GM composition, especially blautia, roseburia and clostridium, significantly reduced the level of endotoxin and markedly increased the acetic acid in feces. Overall, our results demonstrated that EsM ameliorates HFD-induced obesity and related metabolic disorders, like hyperglycemia and insulin resistance, and is strongly associated with modulating the distribution of GM, enterogenous endotoxin and enteral acetic acid.

SUBMITTER: Wang JH

PROVIDER: S-EPMC5486241 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.

Wang Jing-Hua JH Kim Bong-Soo BS Han Kyungsun K Kim Hojun H

International journal of environmental research and public health 20170523 6

Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including <i>Ephedra sinica</i> (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via ...[more]

PMID: 28545248

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Project description:Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months. At the end of 5-month HFD feeding, cardiac function was evaluated using echocardiography. Cardiomyocytes were isolated and contractile properties were measured. Immunofluorescence was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from isolated macrophages were collected to measure the concentrations of pro-inflammatory cytokines using ELISA kits. Western immunoblotting analyses were performed on heart tissue homogenates and isolated macrophages to explore the underlying signaling mechanism(s). CARD9 knockout alleviated HFD-induced insulin resistance and glucose intolerance, prevented myocardial dysfunction with preserved cardiac fractional shortening and cardiomyocyte contractile properties. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart with reduced myocardium-, plasma-, and macrophage-derived cytokines including IL-6, IL-1β and TNFα. Finally, CARD9 knockout abrogated the increase of p38 MAPK phosphorylation, the decrease of LC3BII/LC3BI ratio and the up-regulation of p62 expression in the heart induced by HFD feeding and restored cardiac autophagy signaling. In conclusion, CARD9 knockout ameliorates myocardial dysfunction associated with HFD-induced obesity, potentially through reduction of macrophage infiltration, suppression of p38 MAPK phosphorylation, and preservation of autophagy in the heart.

Project description:Background: Accumulating data support the fact that the gut microbiota plays an important role in the progression of obesity and its related metabolic disease. Sex-related differences are an important consideration in the study of gut microbiota. Polyphenols can regulate gut microbiota, thereby improving obesity and its associated complications. There have been no studies conducted on the ability of honokiol (HON, an extract from Chinese herbal medicine) to regulate gut microbiota. The aim of this study was to examine whether HON supplementation would improve obesity by regulating the gut microbiota and its related metabolite levels, and whether there were sex-based differences in high-fat diet-induced obese mice. Methods: C57BL/6 mice (n = 120) were fed a normal chow diet (ND group), high-fat diet (HFD group), or HFD plus HON at 200, 400, and 800 mg/kg BW for 8 weeks. Body weight, adipose tissue weight, adipocyte diameter, insulin resistance, blood lipid and serum inflammatory cytokines, gut microbiota, and its metabolite were examined at the end of the experiment. Results: The HON supplementation reduced body weight, adipose tissue weight, adipocyte diameter, insulin resistance, blood lipid, and serum inflammatory cytokine levels in HFD-fed mice, and this effect was significant in the high-dose group. In addition, HON not only reversed gut disorders in HFD-fed mice, such as by enhanced the abundance of Akkermansia and short-chain fatty acids (SCFAs) producing Bacteroides and reduced Oscillospira, but also improved the SCFAs and endotoxin (LPS) levels, although there were sex-based differences. The correlation between several specific genera and obesity-related indexes was revealed through Spearman's correlation analysis. Moreover, HON may have dose-dependent effects on regulating gut microbiota to alleviate obesity. Conclusions: These findings suggest that HON can prevent diet-induced obesity and its associated diseases by regulating the gut microbiota and improving microbial metabolite levels. Moreover, our findings indicate that sex may be an important factor affecting HON activity.

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Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.

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Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.

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