Regulation of hepatokine gene expression in response to fasting and feeding : influence of PPAR-α and insulin-dependent signalling in hepatocytes

• Main Authors: Smati, S., Régnier, M., Fougeray, T., Polizzi, A., Fougerat, A., Lasserre, F., Lukowicz, C., Tramunt, B., Guillaume, M., Burnol, A.-F., Postic, C., Wahli, Walter, Montagner, A., Gourdy, P., Guillou, H.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Medicine; Hepatokines; Insulin Receptor
• Online Access: https://hdl.handle.net/10356/144804
• Institution: Nanyang Technological University

Aim – In hepatocytes, the peroxisome proliferator-activated receptor (PPAR)-a 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-a (Ppara hep/) and IR (IRhep/) null mice. Methods – Pparahep/ 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-a is essential for regulating fasting-induced Fgf21 and Angptl4 expression. In mice lacking PPAR-a, 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. C 2019 Elsevier Masson S