Insulin activates hepatic Wnt/β-catenin signaling through stearoyl-CoA desaturase 1 and Porcupine

Autor: Cabrae, Régine, Dubuquoy, Céline, Caüzac, Michèle, Morzyglod, Lucille, Guilmeau, Sandra, Noblet, Bénédicte, Fève, Bruno, Postic, Catherine, Burnol, Anne-Francoise, Moldes, Marthe
Přispěvatelé: Bodescot, Myriam, BLANC - Dialogues génétiques et fonctionnels permettant à la signalisation Wnt/beta-caténine de contrôler la balance énergétique dans le foie - - WNT-METABOLIV2010 - ANR-10-BLAN-1116 - BLANC - VALID, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Mice used in this study were housed in an animal facility equipped with the help of the Région Ile de France. R.C. was a recipient of doctoral fellowship from CORDDIM, Ile de France. C.D. and L.M. were recipients of doctoral fellowship from the Ministère de l’Enseignement Supérieur et de la Recherche. C.D. was a recipient from the Fondation pour la Recherche Médicale (Bourse médico-scientifique). This work was performed at the Cochin Institute within the Département Hospitalo-Universitaire (DHU) AUToimmune and HORmonal diseases and was supported by grants from the Fondation pour la Recherche Médicale (FRM Labélisation Équipe, DEQ. 20150331744), from the Agence Nationale de la Recherche (ANR WNT-METABOLIV), from University Paris Descartes and Sorbonne Université, and from INSERM and CNRS., ANR-10-BLAN-1116,WNT-METABOLIV,Dialogues génétiques et fonctionnels permettant à la signalisation Wnt/beta-caténine de contrôler la balance énergétique dans le foie(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP]
Rok vydání: 2018
Předmět:
Zdroj: Scientific Reports
Scientific Reports, 2020, 10 (1), pp.5186. ⟨10.1038/s41598-020-61869-4⟩
Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.5186. ⟨10.1038/s41598-020-61869-4⟩
Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
ISSN: 2045-2322
Popis: International audience; The Wnt/β-catenin pathway plays a pivotal role in liver structural and metabolic homeostasis. Wnt activity is tightly regulated by the acyltransferase Porcupine through the addition of palmitoleate. Interestingly palmitoleate can be endogenously produced by the stearoyl-CoA desaturase 1 (SCD1), a lipogenic enzyme transcriptionally regulated by insulin. This study aimed to determine whether nutritional conditions, and insulin, regulate Wnt pathway activity in liver. An adenoviral TRE-Luciferase reporter was used as a readout of Wnt/β-catenin pathway activity, in vivo in mouse liver and in vitro in primary hepatocytes. Refeeding enhanced TRE-Luciferase activity and expression of Wnt target genes in mice liver, revealing a nutritional regulation of the Wnt/β-catenin pathway. This effect was inhibited in liver specific insulin receptor KO (iLIRKO) mice and upon wortmannin or rapamycin treatment. Overexpression or inhibition of SCD1 expression regulated Wnt/β-catenin activity in primary hepatocytes. Similarly, palmitoleate added exogenously or produced by SCD1-mediated desaturation of palmitate, induced Wnt signaling activity. Interestingly, this effect was abolished in the absence of Porcupine, suggesting that both SCD1 and Porcupine are key mediators of insulin-induced Wnt/β-catenin activity in hepatocytes. Altogether, our findings suggest that insulin and lipogenesis act as potential novel physiological inducers of hepatic Wnt/β-catenin pathway.
Databáze: OpenAIRE
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