Ginsenoside Rg3 Induces Browning of 3T3-L1 Adipocytes by Activating AMPK Signaling.

Kyungtae Kim,Ki Hong Nam,Jeung-Whan Han,Jong Woo Park,Jaecheol Lee,Sang Ah Yi

doi:10.3390/nu12020427

Abstract

Ginsenoside Rg3, one of the major components in Panax ginseng, has been reported to possess several therapeutic effects including anti-obesity properties. However, its effect on the browning of mature white adipocytes as well as the underlying mechanism remains poorly understood. In this study, we suggested a novel role of Rg3 in the browning of mature 3T3-L1 adipocytes by upregulating browning-related gene expression. The browning effects of Rg3 on differentiated 3T3-L1 adipocytes were evaluated by analyzing browning-related markers using quantitative PCR, immunoblotting, and immunostaining. In addition, the size and sum area of lipid droplets in differentiated 3T3-L1 adipocytes were measured using Oil-Red-O staining. In mature 3T3-L1 adipocytes, Rg3 dose-dependently induced the expression of browning-related genes such as Ucp1, Prdm16, Pgc1α, Cidea, and Dio2. Moreover, Rg3 induced the expression of beige fat-specific genes (CD137 and TMEM26) and lipid metabolism-associated genes (FASN, SREBP1, and MCAD), which indicated the activation of lipid metabolism by Rg3. We also demonstrated that activation of 5’ adenosine monophosphate-activated protein kinase (AMPK) is required for Rg3-mediated up-regulation of browning gene expression. Moreover, Rg3 inhibited the accumulation of lipid droplets and reduced the droplet size in mature 3T3-L1 adipocytes. Taken together, this study identifies a novel role of Rg3 in browning of white adipocytes, as well as suggesting a potential mechanism of an anti-obesity effect of Panax ginseng.

Highlights

Obesity is medically defined as significantly increased body weight, especially increased portion of white adipose tissue (WAT), which can be associated with several disorders [1]
To test whether Rg3 can induce beige adipocyte-like features in differentiated 3T3-L1 adipocytes, we investigated the mRNA levels of beige adipocyte-specific markers CD137 and TMEM26, which were found to be increased by Rg3 treatment (Figure 1E)
These results suggest that Rg3 can decrease the expression of white adipocyte marker genes, as well as up-regulate the lipid metabolism in 3T3-L1 adipocytes

Summary

Introduction

Obesity is medically defined as significantly increased body weight, especially increased portion of white adipose tissue (WAT), which can be associated with several disorders [1]. As obesity is mainly caused by chronically higher food intake than total energy expenditure, maintaining a proper energy balance is important in the treatment of obesity [2]. Approved anti-obesity drugs by the U.S. Food and Drug Administration (FDA) inhibit the energy intake either by suppressing the intestinal fat absorption or by repressing appetite; they often elicit serious side effects, such as depression, oily bowel movements, and steatorrhea [3]. Since the discovery of active brown adipose tissue (BAT) in humans [5], the therapeutic interest concerning browning of white adipose tissue (WAT)

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Discussion

Conclusion