S Smati1, M Régnier2, T Fougeray2, A Polizzi2, A Fougerat2, F Lasserre2, C Lukowicz2, B Tramunt3, M Guillaume3, A-F Burnol4, C Postic4, W Wahli5, A Montagner3, P Gourdy6, H Guillou7. 1. UMR 1331, Institut National de la Recherche Agronomique (INRA), Toxalim (Research Centre in Food Toxicology), 180, chemin de Tournefeuille, 1331 Toulouse, France; UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse, Institut National de la Santé et de la Recherche Médicale (Inserm), 31000 Toulouse, France. 2. UMR 1331, Institut National de la Recherche Agronomique (INRA), Toxalim (Research Centre in Food Toxicology), 180, chemin de Tournefeuille, 1331 Toulouse, France. 3. UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse, Institut National de la Santé et de la Recherche Médicale (Inserm), 31000 Toulouse, France. 4. Institut National de la Santé et de la Recherche Médicale (INSERM U1016), Institut Cochin, 75014 Paris, France; CNRS UMR 8104, 75014 Paris, France; University of Paris Descartes, Sorbonne Paris Cité, 75005 Paris, France. 5. UMR 1331, Institut National de la Recherche Agronomique (INRA), Toxalim (Research Centre in Food Toxicology), 180, chemin de Tournefeuille, 1331 Toulouse, France; Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, 11 Mandalay Road, 308232 Singapore, Singapore; Center for Integrative Genomics, Université de Lausanne, Le Génopode, Lausanne, Switzerland. 6. UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse, Institut National de la Santé et de la Recherche Médicale (Inserm), 31000 Toulouse, France; Diabetology Department, CHU de Toulouse, 31000 Toulouse, France. 7. UMR 1331, Institut National de la Recherche Agronomique (INRA), Toxalim (Research Centre in Food Toxicology), 180, chemin de Tournefeuille, 1331 Toulouse, France. Electronic address: herve.guillou@inra.fr.
Abstract
AIM: In hepatocytes, the peroxisome proliferator-activated receptor (PPAR)-α and insulin receptor (IR) are critical for transcriptional responses to fasting and feeding, respectively. The present report analyzes the effects of nutritional status (fasting vs feeding) on the expression of a large panel of hepatokines in hepatocyte-specific PPAR-α (Pparαhep-/-) and IR (IRhep-/-) null mice. METHODS: Pparαhep-/- and IRhep-/- mice, and their wild-type littermates, were subjected to fasting or feeding metabolic challenges, then analyzed for hepatokine gene expression. Experiments were conducted in mice of both genders. RESULTS: Our data confirmed that PPAR-α is essential for regulating fasting-induced Fgf21 and Angptl4 expression. In mice lacking PPAR-α, fasting led to increased Igfbp1 and Gdf15 gene expression. In the absence of hepatic IR, feeding induced overexpression of Igfbp1, follistatin (Fst) and adropin (Enho), and reduced activin E (Inhbe) expression. Gender had only a modest influence on hepatokine gene expression in the liver. CONCLUSION: The present results highlight the potential roles of hepatokines as a class of hormones that substantially influence nutritional regulation in both female and male mice.
AIM: In hepatocytes, the peroxisome proliferator-activated receptor (PPAR)-α and insulin receptor (IR) are critical for transcriptional responses to fasting and feeding, respectively. The present report analyzes the effects of nutritional status (fasting vs feeding) on the expression of a large panel of hepatokines in hepatocyte-specific PPAR-α (Pparαhep-/-) and IR (IRhep-/-) null mice. METHODS: Pparαhep-/- and IRhep-/- mice, and their wild-type littermates, were subjected to fasting or feeding metabolic challenges, then analyzed for hepatokine gene expression. Experiments were conducted in mice of both genders. RESULTS: Our data confirmed that PPAR-α is essential for regulating fasting-induced Fgf21 and Angptl4 expression. In mice lacking PPAR-α, fasting led to increased Igfbp1 and Gdf15 gene expression. In the absence of hepatic IR, feeding induced overexpression of Igfbp1, follistatin (Fst) and adropin (Enho), and reduced activin E (Inhbe) expression. Gender had only a modest influence on hepatokine gene expression in the liver. CONCLUSION: The present results highlight the potential roles of hepatokines as a class of hormones that substantially influence nutritional regulation in both female and male mice.
Authors: Úrsula Martínez-Garza; Daniel Torres-Oteros; Alex Yarritu-Gallego; Pedro F Marrero; Diego Haro; Joana Relat Journal: Int J Mol Sci Date: 2019-09-21 Impact factor: 5.923