Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-? and insulin-dependent signalling in hepatocytes - 22/04/20

Doi : 10.1016/j.diabet.2019.05.005

S. Smati ^a,^b, M. Régnier ^a, T. Fougeray ^a, A. Polizzi ^a, A. Fougerat ^a, F. Lasserre ^a, C. Lukowicz ^a, B. Tramunt ^b, M. Guillaume ^b, A.-F. Burnol ^c,^d,^e, C. Postic ^c,^d,^e, W. Wahli ^a,^f,^g, A. Montagner ^b, P. Gourdy ^b,^h, H. Guillou ^a,⁎
^a UMR 1331, Institut National de la Recherche Agronomique (INRA), Toxalim (Research Centre in Food Toxicology), 180, chemin de Tournefeuille, 1331 Toulouse, France
^b 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
^c Institut National de la Santé et de la Recherche Médicale (INSERM U1016), Institut Cochin, 75014 Paris, France
^d CNRS UMR 8104, 75014 Paris, France
^e University of Paris Descartes, Sorbonne Paris Cité, 75005 Paris, France
^f Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, 11 Mandalay Road, 308232 Singapore, Singapore
^g Center for Integrative Genomics, Université de Lausanne, Le Génopode, Lausanne, Switzerland
^h Diabetology Department, CHU de Toulouse, 31000 Toulouse, France

^⁎Corresponding author.

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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 (Pparα ^hep−/−) and IR (IR^hep−/−) null mice.

Methods

Pparα^hep−/− and IR^hep−/− 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.

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Keywords : Hepatokines, Insulin receptor, Nutritional regulation, PPAR-α

Plan

Introduction

Materials and methods

Mice

Immunoblotting

Blood and tissue samples

Gene expression analyses

Biochemical analyses

Measurement of blood glucose and ketone bodies

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Vol 46 - N° 2

P. 129-136 - avril 2020 Retour au numéro

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Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-? and insulin-dependent signalling in hepatocytes - 22/04/20

Abstract

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Methods

Results

Conclusion

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