Abstract
Gynostemma pentaphyllum is widely used in Asia as a herbal medicine to treat type 2 diabetes, dyslipidemia, and inflammation. Here, we investigated the anti-obesity effect and underlying mechanism of G. pentaphyllum extract (GPE) enriched in gypenoside L, gypenoside LI, and ginsenoside Rg3 and obtained using a novel extraction method. Five-week-old male C57BL/6N mice were fed a control diet (CD), high-fat diet (HFD), HFD + 100 mg/kg body weight (BW)/day GPE (GPE 100), HFD + 300 mg/kg BW/day GPE (GPE 300), or HFD + 30 mg/kg BW/day Orlistat (Orlistat 30) for 8 weeks. The HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, and adipocyte hypertrophy compared to the CD group; but GPE inhibited those increases. GPE reduced serum levels of triglyceride, total cholesterol, and LDL-cholesterol, without affecting HDL-cholesterol. GPE significantly increased AMPK activation and suppressed adipogenesis by decreasing the mRNA expression of CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP1c), PPARγ coactivator-1α, fatty acid synthase (FAS), adipocyte protein 2 (AP2), and sirtuin 1 (SIRT1) and by increasing that of carnitine palmitoyltransferase (CPT1) and hormone- sensitive lipase (HSL). This study demonstrated the ameliorative effect of GPE on obesity and elucidated the underlying molecular mechanism.
Highlights
The prevalence of obesity has increased worldwide over the past 50 years and has reached pandemic levels
Consumption of high-fat diet (HFD) for eight weeks caused significant increases in body weight (Table 2), but mean body weight gain and fat mass percentage were significantly lower in the G. pentaphyllum extract (GPE)-treated groups than in the HFD group
Our results indicate that the downregulation of transcription factors such as CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), and SREBP-1c, followed by the downregulation of fatty acid synthase (FAS) and aP2 and the upregulation of CPT1 and hormone- sensitive lipase (HSL), resulting from GPE treatment are part of the mechanism by which
Summary
The prevalence of obesity has increased worldwide over the past 50 years and has reached pandemic levels. Once considered a problem only in high-income countries, obesity is dramatically on the rise in low- and middle-income countries. Obesity is a major life-threatening health problem because it substantially increases the risk of various chronic diseases, such as diabetes, cardiovascular diseases, and cancers, contributing to a decline in both quality of life and life expectancy [1,2,3]. The prevention and treatment of obesity are extremely important. Several anti-obesity drugs have been marketed in the last few years but have been successively withdrawn because of serious adverse effects. A few drugs are currently prescribed for treating obesity [4,5,6]
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