ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

In hepatocytes, peroxisome proliferator-activated receptor alpha (PPAR alpha) 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 PPAR alpha deletion in hepatocytes. Adipose tissue lipolysis induced by activation of the beta(3)-adrenergic receptor also triggers such PPAR alpha-dependent responses not only in the liver but also in brown adipose tissue (BAT). Intact PPAR alpha activity in hepatocytes is required for the cross-talk between adipose tissues and the liver during fat mobilization.

Automated summary

In hepatocytes, PPAR alpha is important for maintaining homeostasis during fasting, and the absence of ATGL in adipocytes impairs the production of ketone bodies and FGF21 during fasting. Liver gene expression analysis reveals that these fasting-induced genes are sensitive to both ATGL deletion in adipocytes and PPAR alpha deletion in hepatocytes. Activation of the beta(3)-adrenergic receptor induces PPAR alpha-dependent responses not only in the liver but also in BAT. Intact PPAR alpha activity in hepatocytes is necessary for the interplay between adipose tissues and the liver during fat mobilization.