Alisol A attenuates high-fat-diet-induced obesity and metabolic disorders via the AMPK/ACC/SREBP-1c pathway

J Cell Mol Med. 2019 Aug;23(8):5108-5118. doi: 10.1111/jcmm.14380. Epub 2019 May 29.

Abstract

Obesity and its associated metabolic disorders such as diabetes, hepatic steatosis and chronic heart diseases are affecting billions of individuals. However there is no satisfactory drug to treat such diseases. In this study, we found that alisol A, a major active triterpene isolated from the Chinese traditional medicine Rhizoma Alismatis, could significantly attenuate high-fat-diet-induced obesity. Our biochemical detection demonstrated that alisol A remarkably decreased lipid levels, alleviated glucose metabolism disorders and insulin resistance in high-fat-diet-induced obese mice. We also found that alisol A reduced hepatic steatosis and improved liver function in the obese mice model.In addition, protein expression investigation revealed that alisol A had an active effect on AMPK/ACC/SREBP-1c pathway. As suggested by the molecular docking study, such bioactivity of alisol A may result from its selective binding to the catalytic region of AMPK.Therefore, we believe that Alisol A could serve as a promising agent for treatment of obesity and its related metabolic diseases.

Keywords: AMPK/ACC/SREBP-1c; alisol A; hepatic steatosis; metabolism dysfunction; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Acetyl-CoA Carboxylase / genetics*
  • Animals
  • Cholestenones / pharmacology*
  • Diet, High-Fat / adverse effects
  • Humans
  • Insulin Resistance / genetics
  • Lipid Metabolism / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / etiology
  • Metabolic Diseases / genetics
  • Metabolic Diseases / pathology
  • Mice
  • Mice, Obese
  • Molecular Docking Simulation
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / pathology
  • Obesity / drug therapy*
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / pathology
  • Protein Kinases / genetics*
  • Signal Transduction / drug effects
  • Sterol Regulatory Element Binding Protein 1 / genetics*

Substances

  • Cholestenones
  • Sterol Regulatory Element Binding Protein 1
  • alisol A
  • Protein Kinases
  • AMP-Activated Protein Kinase Kinases
  • ACACA protein, human
  • Acetyl-CoA Carboxylase