Genetic deletion of β 2 adrenergic receptors exacerbates hepatocellular lipid accumulation in high-fat diet mice

Biochem Biophys Res Commun. 2019 Mar 26;511(1):73-78. doi: 10.1016/j.bbrc.2019.02.037. Epub 2019 Feb 13.

Abstract

β2 Adrenergic receptors (β2ARs) are G protein-coupled receptors (GPCRs) that are expressed in major insulin target tissues. β2ARs play an important role in the regulation of lipid metabolism during aging; however, little is known about the significance of β2ARs in the pathogenesis of hepatic fat accumulation in high-fat diet (HFD) mice. This study aims to examine the role of β2AR in the development of nonalcoholic fatty liver disease (NAFLD) induced by HFD and the underlying mechanisms. Surprisingly, we found that genetic deletion of β2AR significantly increased the liver weight of mice fed a HFD for 20 weeks compared to that of wild-type (WT) mice. Moreover, genetic deletion of β2AR could aggravate HFD-induced liver lipid accumulation and liver injury in mice. Mechanistically, we demonstrated that β2AR deletion significantly activated PPARγ/CD36 signaling via inactivation of the cAMP response element-binding (CREB) protein to facilitate hepatocellular lipid deposition in HFD mice. Together, our results identify β2AR as a plausible therapeutic target for preventing or treating NAFLD.

Keywords: Fatty acid metabolism; High-fat diet; Nonalcoholic fatty liver; β(2) adrenergic receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects
  • Gene Deletion*
  • Lipid Metabolism
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Organ Size
  • Receptors, Adrenergic, beta-2 / genetics*

Substances

  • ADRB2 protein, mouse
  • Receptors, Adrenergic, beta-2