Zinc oxide nanoparticles attenuate hepatic steatosis development in high-fat-diet fed mice through activated AMPK signaling axis

Nanomedicine. 2019 Apr;17:210-222. doi: 10.1016/j.nano.2019.01.013. Epub 2019 Jan 30.

Abstract

Insulin resistance is thought to be a common link between obesity and Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD has now reached epidemic status worldwide and identification of molecules or pathways as newer therapeutic strategies either to prevent or overcome insulin resistance seems critical. Dysregulated hepatic lipogenesis (DNL) is a hallmark of NAFLD in humans and rodents. Therefore, reducing DNL accretion may be critical in the development of therapeutics of NAFLD. In our in vivo model (high-fat-diet fed [HFD] obese mice) we found Zinc oxide nanoparticles (ZnO NPs) significantly decreased HFD-induced hepatic steatosis and peripheral insulin resistance. This protective mechanism of ZnO NPs was signaled through hepatic SIRT1-LKB1-AMPK which restricted SREBP-1c within the cytosol limiting its transcriptional ability and thereby ameliorating HFD mediated DNL. These observations indicate that ZnO NP can serve as a therapeutic strategy to improve the physiological homeostasis during obesity and its associated metabolic abnormalities.

Keywords: AMPK; LKB1; Non-alcoholic fatty liver disease; SIRT1; SREBP1c; ZnO NP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Diet, High-Fat / adverse effects
  • Enzyme Activators / therapeutic use*
  • Hep G2 Cells
  • Humans
  • Insulin Resistance
  • Liver / drug effects
  • Liver / metabolism
  • Mice, Inbred C57BL
  • Nanoparticles / therapeutic use*
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Signal Transduction / drug effects
  • Zinc Oxide / therapeutic use*

Substances

  • Enzyme Activators
  • AMP-Activated Protein Kinases
  • Zinc Oxide