Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway

Toxicol Appl Pharmacol. 2016 Aug 1;304:99-109. doi: 10.1016/j.taap.2016.05.011. Epub 2016 May 18.

Abstract

Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.

Keywords: Curcumin; Insulin resistance; Obesity; SREBPs; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Animals
  • Blood Glucose
  • Cholesterol / biosynthesis
  • Curcumin / pharmacology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diet, High-Fat
  • Down-Regulation
  • Energy Metabolism / drug effects
  • Insulin Resistance / physiology*
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / physiopathology*
  • Sterol Regulatory Element Binding Proteins / antagonists & inhibitors*
  • Triglycerides / biosynthesis
  • Weight Gain / drug effects

Substances

  • Blood Glucose
  • Sterol Regulatory Element Binding Proteins
  • Triglycerides
  • Cholesterol
  • Curcumin