Cell Rep. 2022 Jun 7;39(10):110910. doi: 10.1016/j.celrep.2022.110910.
Anne Fougerat 1, Gabriele Schoiswohl 2, Arnaud Polizzi 1, Marion Régnier 1, Carina Wagner 3, Sarra Smati 4, Tiffany Fougeray 1, Yannick Lippi 1, Frederic Lasserre 1, Ilyès Raho 5, Valentine Melin 1, Blandine Tramunt 6, Raphaël Métivier 7, Caroline Sommer 1, Fadila Benhamed 8, Chantal Alkhoury 9, Franziska Greulich 10, Céline Jouffe 11, Anthony Emile 1, Michael Schupp 12, Pierre Gourdy 6, Patricia Dubot 13, Thierry Levade 13, Delphine Meynard 14, Sandrine Ellero-Simatos 1, Laurence Gamet-Payrastre 1, Ganna Panasyuk 9, Henriette Uhlenhaut 15, Ez-Zoubir Amri 16, Céline Cruciani-Guglielmacci 5, Catherine Postic 8, Walter Wahli 17, Nicolas Loiseau 1, Alexandra Montagner 18, Dominique Langin 19, Achim Lass 20, Hervé 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.
- PMID: 35675775
- DOI: 10.1016/j.celrep.2022.110910