ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

Cell Rep. 2022 Jun 7;39(10):110910. doi: 10.1016/j.celrep.2022.110910.

Abstract

In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting. Liver gene expression analysis highlights a set of fasting-induced genes sensitive to both ATGL deletion in adipocytes and PPARα deletion in hepatocytes. Adipose tissue lipolysis induced by activation of the β3-adrenergic receptor also triggers such PPARα-dependent responses not only in the liver but also in brown adipose tissue (BAT). Intact PPARα activity in hepatocytes is required for the cross-talk between adipose tissues and the liver during fat mobilization.

Keywords: ATGL; CP: Metabolism; FGF21; PPARα; fasting; ketogenesis; lipolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / metabolism
  • Hepatocytes / metabolism
  • Ketone Bodies / metabolism
  • Lipolysis* / physiology
  • PPAR alpha* / metabolism

Substances

  • Ketone Bodies
  • PPAR alpha