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 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

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.

• PMID: 35675775
• DOI: 10.1016/j.celrep.2022.110910