Clusterin overexpression protects against western diet-induced obesity and NAFLD

Sci Rep. 2020 Oct 15;10(1):17484. doi: 10.1038/s41598-020-73927-y.


Obesity is a significant risk factor for various metabolic diseases and is closely related to non-alcoholic fatty liver disease (NAFLD) characterized by inflammation and oxidative stress. Clusterin is a multi-functional protein that is up-regulated in the pathogenesis of various metabolic diseases, including obesity and NAFLD. Our previous studies indicated that hepatocyte-specific overexpression of clusterin alleviates methionine choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH) by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Here we generated transgenic mice with whole-body clusterin overexpression (wCLU-tg) and investigated the role of clusterin in Western diet-induced obesity and NAFLD. We confirmed that obesity parameters and the spectrum of NAFLD of wCLU-tg mice were improved compared to wild type mice. Contrarily, clusterin deficiency deteriorated metabolic disruptions. We also found that clusterin activates target molecules for obesity and NAFLD, namely Nrf2 and AMPK, suggesting that clusterin protects against Western diet-induced obesity and NAFLD by activating Nrf2 and AMPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Alleles
  • Animals
  • Cell Line
  • Cell Nucleus / metabolism
  • Clusterin / metabolism*
  • Cytosol / metabolism
  • Diet, Western / adverse effects
  • Disease Models, Animal
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2 / metabolism
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / etiology
  • Obesity / metabolism*
  • Oxidative Stress
  • Risk Factors


  • CLU protein, human
  • Clu protein, mouse
  • Clusterin
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • AMP-Activated Protein Kinases