ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

doi:10.1016/j.celrep.2022.110910

. 2022 Jun 7;39(10):110910.

doi: 10.1016/j.celrep.2022.110910.

ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

Anne Fougerat¹, Gabriele Schoiswohl², Arnaud Polizzi¹, Marion Régnier¹, Carina Wagner³, Sarra Smati⁴, Tiffany Fougeray¹, Yannick Lippi¹, Frederic Lasserre¹, Ilyès Raho⁵, Valentine Melin¹, Blandine Tramunt⁶, Raphaël Métivier⁷, Caroline Sommer¹, Fadila Benhamed⁸, Chantal Alkhoury⁹, Franziska Greulich¹⁰, Céline Jouffe¹¹, Anthony Emile¹, Michael Schupp¹², Pierre Gourdy⁶, Patricia Dubot¹³, Thierry Levade¹³, Delphine Meynard¹⁴, Sandrine Ellero-Simatos¹, Laurence Gamet-Payrastre¹, Ganna Panasyuk⁹, Henriette Uhlenhaut¹⁵, Ez-Zoubir Amri¹⁶, Céline Cruciani-Guglielmacci⁵, Catherine Postic⁸, Walter Wahli¹⁷, Nicolas Loiseau¹, Alexandra Montagner¹⁸, Dominique Langin¹⁹, Achim Lass²⁰, Hervé Guillou²¹

Affiliations

¹ Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France.
² Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, 8010 Graz, Austria; BioTechMed-Graz, Graz, Austria; Department of Pharmacology and Toxicology, University of Graz, Humboldtstraße 46/II, 8010 Graz, Austria.
³ Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, 8010 Graz, Austria; BioTechMed-Graz, Graz, Austria.
⁴ Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France; Nantes Université, CHU Nantes, CNRS, INSERM, l'Institut du Thorax, 44000 Nantes, France.
⁵ Université Paris Cité, BFA, UMR 8251, CNRS, 75013 Paris, France.
⁶ Institute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, INSERM, Toulouse III University - Paul Sabatier (UPS), Toulouse, France; Service de Diabétologie, Maladies Métaboliques et Nutrition, CHU de Toulouse, Toulouse, France.
⁷ Institut de Génétique et Développement de Rennes, Université de Rennes, UMR 6290 CNRS, Rennes, France.
⁸ Institut Cochin, Université Paris Cité, CNRS, INSERM, F-75014 Paris, France.
⁹ Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker-Enfants Malades, F-75015 Paris, France.
¹⁰ Metabolic Programming, TUM School of Life Sciences, ZIEL Institute for Food & Health, Gregor-Mendel-Strasse 2, 85354 Freising, Germany.
¹¹ Helmholtz Diabetes Center (IDO, IDC, IDE), Helmholtz Center Munich HMGU, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany.
¹² Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany.
¹³ INSERM U1037, CRCT, Université Paul Sabatier, 31059 Toulouse, France; Laboratoire de Biochimie, CHU Toulouse, Toulouse, France.
¹⁴ Institute of Digestive Health Research, IRSD, INSERM U1220, Toulouse, France.
¹⁵ Metabolic Programming, TUM School of Life Sciences, ZIEL Institute for Food & Health, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; Helmholtz Diabetes Center (IDO, IDC, IDE), Helmholtz Center Munich HMGU, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany.
¹⁶ Université Côte d'Azur, CNRS, INSERM, iBV, Nice, France.
¹⁷ Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France; Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore 308232, Singapore; Center for Integrative Genomics, University of Lausanne, Le Génopode, 1015 Lausanne, Switzerland.
¹⁸ Institute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, INSERM, Toulouse III University - Paul Sabatier (UPS), Toulouse, France.
¹⁹ Institute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, INSERM, Toulouse III University - Paul Sabatier (UPS), Toulouse, France; Laboratoire de Biochimie, CHU Toulouse, Toulouse, France; Academic Institute of France (IUF), Paris, France.
²⁰ Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, 8010 Graz, Austria; BioTechMed-Graz, Graz, Austria. Electronic address: achim.lass@uni-graz.at.
²¹ Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France. Electronic address: herve.guillou@inrae.fr.

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

Free article

ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

Anne Fougerat et al. Cell Rep. 2022.

Free article

. 2022 Jun 7;39(10):110910.

doi: 10.1016/j.celrep.2022.110910.

Authors

Affiliations

¹ Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France.
² Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, 8010 Graz, Austria; BioTechMed-Graz, Graz, Austria; Department of Pharmacology and Toxicology, University of Graz, Humboldtstraße 46/II, 8010 Graz, Austria.
³ Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, 8010 Graz, Austria; BioTechMed-Graz, Graz, Austria.
⁴ Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France; Nantes Université, CHU Nantes, CNRS, INSERM, l'Institut du Thorax, 44000 Nantes, France.
⁵ Université Paris Cité, BFA, UMR 8251, CNRS, 75013 Paris, France.
⁶ Institute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, INSERM, Toulouse III University - Paul Sabatier (UPS), Toulouse, France; Service de Diabétologie, Maladies Métaboliques et Nutrition, CHU de Toulouse, Toulouse, France.
⁷ Institut de Génétique et Développement de Rennes, Université de Rennes, UMR 6290 CNRS, Rennes, France.
⁸ Institut Cochin, Université Paris Cité, CNRS, INSERM, F-75014 Paris, France.
⁹ Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker-Enfants Malades, F-75015 Paris, France.
¹⁰ Metabolic Programming, TUM School of Life Sciences, ZIEL Institute for Food & Health, Gregor-Mendel-Strasse 2, 85354 Freising, Germany.
¹¹ Helmholtz Diabetes Center (IDO, IDC, IDE), Helmholtz Center Munich HMGU, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany.
¹² Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany.
¹³ INSERM U1037, CRCT, Université Paul Sabatier, 31059 Toulouse, France; Laboratoire de Biochimie, CHU Toulouse, Toulouse, France.
¹⁴ Institute of Digestive Health Research, IRSD, INSERM U1220, Toulouse, France.
¹⁵ Metabolic Programming, TUM School of Life Sciences, ZIEL Institute for Food & Health, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; Helmholtz Diabetes Center (IDO, IDC, IDE), Helmholtz Center Munich HMGU, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany.
¹⁶ Université Côte d'Azur, CNRS, INSERM, iBV, Nice, France.
¹⁷ Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France; Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore 308232, Singapore; Center for Integrative Genomics, University of Lausanne, Le Génopode, 1015 Lausanne, Switzerland.
¹⁸ Institute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, INSERM, Toulouse III University - Paul Sabatier (UPS), Toulouse, France.
¹⁹ Institute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, INSERM, Toulouse III University - Paul Sabatier (UPS), Toulouse, France; Laboratoire de Biochimie, CHU Toulouse, Toulouse, France; Academic Institute of France (IUF), Paris, France.
²⁰ Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, 8010 Graz, Austria; BioTechMed-Graz, Graz, Austria. Electronic address: achim.lass@uni-graz.at.
²¹ Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France. Electronic address: herve.guillou@inrae.fr.

PMID: 35675775
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.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

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ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

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Conflict of interest statement

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