Ginsenoside Rb2 Alleviates Obesity by Activation of Brown Fat and Induction of Browning of White Fat.

Ginsenoside Rb2 (Rb2), the most abundant saponin contained in Panax ginseng, has been used to treat variety of metabolic diseases. However, its effects in obesity and potential mechanisms are not well-understood. In the present study, we investigated metabolic performance with a Rb2 supplement in diet-induced obese (DIO) mice, focusing on the effects and mechanisms of Rb2 on brown and beige fat functions. Our results demonstrated that Rb2 effectively reduced body weight, improved insulin sensitivity, as well as induced energy expenditure in DIO mice. Histological and gene analysis revealed that Rb2 induced activation of brown fat and browning of white fat by reducing lipid droplets, stimulating uncoupling protein 1 (UCP1) staining, and increasing expression of thermogenic and mitochondrial genes, which could be recapitulated in 3T3-L1, C3H10T1/2, and primary adipocytes. In addition, Rb2 induced phosphorylation of AMP-activated protein kinase (AMPK) both in vitro and in vivo. These effects were shown to be dependent on AMPK since its inhibitor blocked Rb2 from inducing expressions of Pgc1α and Ucp1. Overall, the present study revealed that Rb2 activated brown fat and induced browning of white fat, which increased energy expenditure and thermogenesis, and consequently ameliorated obesity and metabolic disorders. These suggest that Rb2 holds promise in treating obesity.

Association between skeletal muscle mass to visceral fat area ratio and arterial stiffness in Chinese patients with type 2 diabetes mellitus.

BACKGROUND: The skeletal muscle mass-to-visceral fat area ratio (SVR) has been linked to arterial stiffness in non-diabetic adults. We examined the association between the SVR and arterial stiffness in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with type 2 diabetes mellitus (252 men and 171 women) aged 40-75 years were enrolled and divided into three groups according to SVR tertiles. Arterial stiffness was measured as brachial-ankle pulse wave velocity (baPWV), with baPWV> 1800 mm/s defined as high. Spearman's partial correlation was used to adjust confounding factors. The odds ratio for high baPWV was determined by multiple logistic regression analyses, and receiver-operating characteristic analysis was conducted. RESULTS: SVR was associated with baPWV in Chinese patients with T2DM (Spearman's partial correlation = - 0.129, P < 0.01). SVR was found to be significantly associated with baPWV on multiple logistic regression analysis. Patients in the lower SVR tertiles had a higher OR than did those in the higher SVR tertiles, after adjusting for multiple covariates (Q1: OR = 4.33 in men and 4.66 in women; Q3: OR = 1). The area under the curve for SVR was significantly greater than that for appendicular skeletal muscle (ASM), ASM/height2, and visceral fat area (VAF) for identifying high baPWV (0.747 in men and 0.710 in women). The optimal cutoffs values of SVR for detecting high baPWV were 191.7 g/cm2 for men and 157.3 g/cm2 for women. CONCLUSIONS: SVR has an independent, negative association with arterial stiffness, and is a better risk-assessment tool than ASM, ASM/height2, and VFA in clinical practice to identify patients with type 2 diabetes at high cardiovascular risk.

Ginsenoside Rb2 promotes glucose metabolism and attenuates fat accumulation via AKT-dependent mechanisms.

Ginsenosides, the major active constituents of ginseng, have been demonstrated possess anti-diabetic, anti-inflammatory effects. Ginsenoside Rb2 (Rb2) is the most abundant saponin in Panax ginseng, this study investigates the role of Rb2 in the anti-hyperglycemic mechanism of insulin-sensitive cell lines 3T3-L1 adipocytes as well as high fat diet-induced obesity mice. Glucose uptake of 3T3-L1 adipocytes was measured. The insulin signaling cascade, including insulin AKT, insulin receptor (IR) beta-subunit, IR substrate (IRS) -1, phosphatidylinositol 3-kinase (PI3K) were also examined. TNF-α-treated 3T3-L1 adipocytes were used as an insulin resistant model in which p-AKT, c-Jun NH2-terminal kinase (JNK), MAPK, and nuclear factor (NF) -κB signaling cascades were examined. As an in vivo study, C57BL/6J mice were fed with a high-fat diet for 9 weeks, with or without Rb2 supplementation. Then we investigated the effects of Rb2 on glycometabolism in these high fat diet-induced obesity mice. Our results demonstrate Rb2 increases glucose uptake in 3T3-L1 adipocytes, independent of insulin receptor ß-subunit (IRß) and principally through the insulin receptor substrate (IRS)-1-phosphatidylinositol 3-kinase (PI3K)-AKT/PKB pathway. Rb2 inhibited TNF-α-induced activation of MAPK and nuclear factor (NF)-κB signaling pathway as well as the expression of inflammatory factors. In high fat diet-induced obesity mice, Rb2 attenuated fat mass and regulated insulin resistance. In mouse adipose tissue, Rb2 phosphorylation of AKT was correlated with glycometabolism. Furthermore, Rb2 attenuates insulin resistance in 3T3-L1 adipocytes, reduces fat mass, and improves insulin sensitivity in high fat diet-obesity mice.