Effects of ginsenoside Rb1 on skeletal muscle insulin resistance and adenosine monophosphate-activated protein kinase signaling pathway in obese mice

Abstract

Objectives: The objective of the study is to observe the effects of ginsenoside Rb1 on indexes of body weight, body composition, blood lipid, skeletal muscle endurance, and insulin sensitivity in obese mice, probe into its pharmacological action, and further explore its effects on adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in skeletal muscle. Materials and Methods: Eight-week-old C57BL/6J mice were fed with high-fat diet for 12 weeks to establish obese mouse model. The model-establishment obese mice were randomly divided into three groups including model control group, metformin group, and ginsenoside Rb1 group. In the normal control group, normal diet was administered. The intervention period was 8 weeks. Body weight and food intake of the mice were measured regularly every week. The treadmill test was performed at weeks 3 and 7, and the oral glucose tolerance test was carried out at weeks 4 and 8. Body composition of the mice was detected by applying NMR Animal Body Composition Analyzer at week 8. Four parameters of blood lipids and free fatty acid (FFA) levels were detected. The mRNA expression of AMPKα and proliferator-activated receptor gamma coactivator-1α (PGC-1α) in skeletal muscle was examined by real-time fluorescence quantitative polymerase chain reaction, and the influence of ginsenoside Rb1 on protein expression of AMPKα, p-AMPKα, and PGC-1α was observed by western blotting. Results: The body weight (since the 5th week of drug administration) and food intake of the mice in the ginsenoside Rb1 group were significantly lower than those in the model control group (P < 0.05) in a time-dependent manner. Ginsenoside Rb1 could significantly reduce the levels of triglyceride and low-density lipoprotein cholesterol, while increase the high-density lipoprotein cholesterol level (P < 0.05). In addition, ginsenoside Rb1 could reduce the serum FFA level (P < 0.05). After the administration of ginsenoside Rb1 for 8 weeks, the body fat mass of obese mice decreased and the lean mass increased (P < 0.05). The skeletal muscle endurance and the oral glucose tolerance of the obese mice improved using ginsenoside Rb1. At the molecular level, ginsenoside Rb1 could up-regulate the mRNA and protein expression of AMPKα in skeletal muscle, and increase the content of p-AMPK protein significantly (P < 0.01). At the same time, the mRNA and protein level of PGC-1α was also un-regulated, correspondingly (P < 0.01). Conclusion: Ginsenoside Rb1 exerts effects on reducing body weight, decreasing blood lipid levels, enhancing the skeletal muscle endurance, and increasing the insulin sensitivity in obese mice by activating the related proteins in AMPK signaling pathway in skeletal muscle.

Keywords

• Adenosine monophosphate-activated protein kinase signaling pathway
• ginsenoside Rb1
• insulin resistance
• obesity
• skeletal muscle