Abstract
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.
Highlights
Obesity, manifested as excessive fat accumulation, has become a global epidemic disorder that contributes to the development of several chronic diseases, including diabetes, cardiovascular diseases, and metabolic syndrome [1]
As the central player in energy homeostasis, adipose tissues could be divided into the following subsets: white adipose tissue (WAT) which is characterized by large unilocular lipid-droplets-containing and functions as an active endocrine organ to regulate diverse activities, such as insulin sensitivity and brown adipose tissue (BAT) which dissipates energy as heat via the uncoupling protein 1 (UCP1) [2]
We found that diet-induced obese (DIO) mice supplemented with Rb2 had better tolerance to glucose load and were more sensitive to insulin addition, which were shown in Glucose Tolerance Test (GTT) and Insulin Tolerance Test (ITT) analyses (Figures 1C–F, Figures S1E–S1H)
Summary
Obesity, manifested as excessive fat accumulation, has become a global epidemic disorder that contributes to the development of several chronic diseases, including diabetes, cardiovascular diseases, and metabolic syndrome [1]. In addition to the direct regulation of Treatment of Obesity With Ginsenoside Rb2 energy homeostasis, brown and beige fats function as metabolic sinks to modulate glucose and lipid metabolism, independent of their effects on weight loss [6]. These functional brown and beige adipocytes are found to exist in adults while obese and aging individuals exhibit functional defects in these adipocytes [7,8,9], suggesting the importance of targeting brown and beige adipocytes for treating obesity and metabolic disorders
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