Calebin-A Inhibits Adipogenesis and Hepatic Steatosis in High-Fat Diet-Induced Obesity via Activation of AMPK Signaling

Mol Nutr Food Res. 2015 Oct;59(10):1883-95. doi: 10.1002/mnfr.201400809. Epub 2015 Jul 20.

Abstract

Scope: Diet-induced obesity and associated nonalcoholic fatty liver disease have increased and become a major health problem worldwide. This study was conducted to investigate the chemopreventive effects of dietary Calebin-A, a curcuminoid, on differentiation of 3T3-L1 adipocytes and high-fat diet (HFD) induced obesity and hepatic steatosis. Potential mechanisms contributing to these effects were also elucidated.

Methods and results: Calebin-A effectively and dose dependently suppressed accumulation of lipid droplets in adipocytes through the suppression of adipogenic specific factor peroxisome proliferator-activated receptor (PPAR) γ and fatty acid synthase and activated acetyl-CoA carboxylase. Dietary Calebin-A effectively decreased weight gain and relative perigonadal, retroperitoneal, and mesenteric fat weight in HFD-fed mice. Furthermore, Calebin-A markedly reduced hepatic steatosis and the serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, total cholesterol, and triacylglycerol. These effects were associated with the downregulation of PPARγ, sterol regulatory element-binding protein-1, and particularly the activation of AMP-activated protein kinase α signaling found in both adipocytes and liver tissues.

Conclusion: Taken together, these results demonstrated for the first time that Calebin-A suppressed adipocyte differentiation, prevented HFD-induced obesity, and improved hepatic steatosis, suggesting a novel application for the prevention and treatment of obesity and associated nonalcoholic fatty liver disease.

Keywords: 3T3-L1 adipocytes; AMP-activated protein kinase; Adipogenesis; Calebin-A; High-fat diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells / drug effects
  • AMP-Activated Protein Kinases / metabolism*
  • Adipogenesis / drug effects*
  • Adipogenesis / physiology
  • Animals
  • Cell Differentiation / drug effects
  • Cinnamates / pharmacology*
  • Diet, High-Fat / adverse effects
  • Fatty Liver / drug therapy*
  • Fatty Liver / etiology
  • Fatty Liver / pathology
  • Lipolysis / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monoterpenes / pharmacology*
  • Obesity / etiology
  • Obesity / prevention & control*
  • Signal Transduction / drug effects

Substances

  • Cinnamates
  • Monoterpenes
  • calebin-A
  • AMP-Activated Protein Kinases