Cell Rep.: co-auth.: W.Wahli

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

ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

Anne Fougerat 1Gabriele Schoiswohl 2Arnaud Polizzi 1Marion Régnier 1Carina Wagner 3Sarra Smati 4Tiffany Fougeray 1Yannick Lippi 1Frederic Lasserre 1Ilyès Raho 5Valentine Melin 1Blandine Tramunt 6Raphaël Métivier 7Caroline Sommer 1Fadila Benhamed 8Chantal Alkhoury 9Franziska Greulich 10Céline Jouffe 11Anthony Emile 1Michael Schupp 12Pierre Gourdy 6Patricia Dubot 13Thierry Levade 13Delphine Meynard 14Sandrine Ellero-Simatos 1Laurence Gamet-Payrastre 1Ganna Panasyuk 9Henriette Uhlenhaut 15Ez-Zoubir Amri 16Céline Cruciani-Guglielmacci 5Catherine Postic 8Walter Wahli 17Nicolas Loiseau 1Alexandra Montagner 18Dominique Langin 19Achim Lass 20Hervé Guillou 21Affiliations expand


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.