Anti-adipogenic Effects and Mechanisms of Ginsenoside Rg3 in Pre-adipocytes and Obese Mice

Longyun Zhang,Xiaoyong Wang,Hongwei Si,Lijuan Zhang

doi:10.3389/fphar.2017.00113

Abstract

Red or black ginseng has been reported more powerful than white/fresh ginseng in dealing with various diseases/conditions including obesity. The major reason is that heating/steaming, the process of making red or black ginseng, produces large amount of bioactive compounds including ginsenoside Rg3 (Rg3), which are trace in fresh or white ginseng. In the present study, Rg3 was applied both in pre-adipocytes and obese mice to investigate the anti-adipogenic effects and relevant mechanisms. Our results show that Rg3 dose-dependently inhibited cell differentiation both in 3T3-L1 cells (30, 50, and 100 μM) and human primary pre-adipocytes (10, 20, and 30 μM). This inhibitory effect is accompanied by the attenuation of the expressions of adipogenic markers including peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein alpha (C/EBP-α), fatty acid synthase (FAS), fatty acid binding protein 4 (FABP4) and perilipin. Although dietary intake of Rg3 (0.1 mg Rg3/kg diet, 8 weeks) did not significantly affect body weight gain, fat pads and food intake as well as of PPAR-γ expression in fat tissues, we found that hepatic PPAR-γ and C/EBP-α protein expressions and hepatic glutathione reductase and glutathione S-transferase, two major antioxidants molecules were significantly reduced by Rg3. These results suggest that ginsenoside Rg3 may be a potential agent in reducing/preventing obesity.

Highlights

Adipogenesis, the process of adipocytes differentiated from pre-adipocytes, plays a key role in the adult obesity development because obese subjects have more fat cells compared to the lean subjects (van Harmelen et al, 2003)
We reported for the first time that ginsenoside Rg3 inhibited pre-adipocyte differentiation in human primary pre-adipocytes (HPAs) at much lower concentrations compared to the concentrations worked in rodent pre-adipocytes 3T3-L1 cells
We found that Rg3 dose-dependently inhibited fat accumulation, expressions of peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein alpha (C/EBP-α), fatty acid synthase (FAS), and perilipin in 3T3-L1 cells

Summary

INTRODUCTION

Adipogenesis, the process of adipocytes differentiated from pre-adipocytes, plays a key role in the adult obesity development because obese subjects have more fat cells compared to the lean subjects (van Harmelen et al, 2003). The adipogenesis and lipogenesis (the process of fatty acid, triglyceride synthesis, and fat drop packaging) are regulated by transcriptional cascades PPAR-γ and CCAAT/enhancer binding proteins (C/EBPs), which are accompanied by a dramatic. Increased C/EBP-α and PPAR-γ induce the expression of genes that are involved in insulin sensitivity, lipogenesis, and lipolysis, including those encoding glucose transporter, FABP4, lipoprotein lipase, perilipin and the secreted factors adiponectin and leptin (Lowe et al, 2011). We found that Rg3 dose-dependently inhibited cell differentiation both in 3T3-L1 cells and HPAs, which was accompanied by the reductions of proteins and mRNA expressions of PPAR-γ, C/EBP-α, FAS, and FABP4. Rg3 reduced hepatic PPAR-γ and C/EBP-α protein expressions in obese mice The changes of these key molecules of adipogenesis provide critical clues for us to understand how Rg3 inhibits fat development in molecular level

MATERIALS AND METHODS

RESULTS

DISCUSSION