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Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet.

ABSTRACT: A low-grade pro-inflammatory state is at the pathogenic core of obesity and type 2 diabetes. We tested the hypothesis that the plant terpenoid compound ginsenoside Rb1 (Rb1), known to exert anti-inflammatory effects, would ameliorate obesity, obesity-associated inflammation and glucose intolerance in the high-fat diet-induced obese mouse model. Furthermore, we examined the effect of Rb1 treatment on central leptin sensitivity and the leptin signaling pathway in the hypothalamus. We found that intraperitoneal injections of Rb1 (14 mg/kg, daily) for 21 days significantly reduced body weight gain, fat mass accumulation, and improved glucose tolerance in obese mice on a HF diet compared to vehicle treatment. Importantly, Rb1 treatment also reduced levels of pro-inflammatory cytokines (TNF-?, IL-6 and/or IL-1?) and NF-?B pathway molecules (p-IKK and p-I?B?) in adipose tissue and liver. In the hypothalamus, Rb1 treatment decreased the expression of inflammatory markers (IL-6, IL-1? and p-IKK) and negative regulators of leptin signaling (SOCS3 and PTP1B). Furthermore, Rb1 treatment also restored the anorexic effect of leptin in high-fat fed mice as well as leptin pSTAT3 signaling in the hypothalamus. Ginsenoside Rb1 has potential for use as an anti-obesity therapeutic agent that modulates obesity-induced inflammation and improves central leptin sensitivity in HF diet-induced obesity.

SUBMITTER: Wu Y

PROVIDER: S-EPMC3968027 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet.

Wu Yizhen Y Yu Yinghua Y Szabo Alexander A Han Mei M Huang Xu-Feng XF

PloS one 20140327 3

A low-grade pro-inflammatory state is at the pathogenic core of obesity and type 2 diabetes. We tested the hypothesis that the plant terpenoid compound ginsenoside Rb1 (Rb1), known to exert anti-inflammatory effects, would ameliorate obesity, obesity-associated inflammation and glucose intolerance in the high-fat diet-induced obese mouse model. Furthermore, we examined the effect of Rb1 treatment on central leptin sensitivity and the leptin signaling pathway in the hypothalamus. We found that in ...[more]

PMID: 24675731

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Project description:Gut microbiota plays an important role in metabolic homeostasis. Previous studies demonstrated that ginsenoside Rb1 might improve obesity-induced metabolic disorders through regulating glucose and lipid metabolism in the liver and adipose tissues. Due to low bioavailability and enrichment in the intestinal tract of Rb1, we hypothesized that modulation of the gut microbiota might account for its pharmacological effects as well. Here, we show that oral administration of Rb1 significantly decreased serum LDL-c, TG, insulin, and insulin resistance index (HOMA-IR) in mice with a high-fat diet (HFD). Dynamic profiling of the gut microbiota showed that this metabolic improvement was accompanied by restoring of relative abundance of some key bacterial genera. In addition, the free fatty acids profiles in feces were significantly different between the HFD-fed mice with or without Rb1. The content of eight long-chain fatty acids (LCFAs) was significantly increased in mice with Rb1, which was positively correlated with the increase of Akkermansia and Parasuttereller, and negatively correlated with the decrease of Oscillibacter and Intestinimonas. Among these eight increased LCFAs, eicosapentaenoic acid (EPA), octadecenoic acids, and myristic acid were positively correlated with metabolic improvement. Furthermore, the colonic expression of the free fatty acid receptors 4 (Ffar4) gene was significantly upregulated after Rb1 treatment, in response to a notable increase of LCFA in feces. These findings suggested that Rb1 likely modulated the gut microbiota and intestinal free fatty acids profiles, which should be beneficial for the improvement of metabolic disorders in HFD-fed mice. This study provides a novel mechanism of Rb1 for the treatment of metabolic disorders induced by obesity, which may provide a therapeutic avenue for the development of new nutraceutical-based remedies for treating metabolic diseases, such as hyperlipidemia, insulin resistance, and type 2 diabetes.

Project description:BackgroundTo observe the effect of ginsenoside Rb1, salvianolic acid B and their combination on glucolipid metabolism and structural changes of gut microbiota.MethodsEight-week-old C57BL/6J mice were fed 45% high-fat diet to induce obesity. The obese mice were randomly divided into four groups, Con group as model control, ginsenoside Rb1 (Rb1) group, salvianolic acid B (SalB) group and ginsenoside Rb1+ salvianolic acid B (Rb1SalB) group. Mice in Rb1, SalB and Rb1SalB group were treated by gavage with ginsenoside Rb1, salvianolic acid B and the combination of the two ingredients, respectively. While mice in Con group were given the same amount of sterile water. The intervention lasted 8 weeks. Body weight and fasting blood glucose were measured every 2 weeks. Oral glucose tolerance test was conducted on the 4th and 8th week of drug intervention. At the end of the experiment, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol and non-esterified fatty acid content as well as glycated hemoglobin were measured and feces were collected for 16S rDNA sequencing.ResultsBoth ginsenoside Rb1 and Rb1SalB combination decreased body weight significantly (P < 0.05). Ginsenoside Rb1, salvianolic acid B and their combination alleviated fasting blood glucose, glycated hemoglobin and blood lipid profiles effectively (P < 0.05, compared with the corresponding indicators in Con group). Oral glucose tolerance test results at the 8th week showed that glucose tolerance was significantly improved in all three treatment groups. Ginsenoside Rb1, salvianolic acid B and their combination reduced the overall diversity of gut microbiota in feces and changed the microbial composition of the obese mice. LDA effect size (LefSe) analysis revealed the key indicator taxa corresponding to the treatment.ConclusionGinsenoside Rb1, salvianolic acid B and their combination could lower blood glucose and lipid level, and improve glucose tolerance of obese mice. The above effect may be at least partially through modulation of gut microbial composition.

Dataset Information

Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet.

Publications

Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet.

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