Cell Rep.: co-auth.: W.Wahli

Cell Rep. 2022 Apr 12;39(2):110674. doi: 10.1016/j.celrep.2022.110674.

The hepatocyte insulin receptor is required to program the liver clock and rhythmic gene expression

Tiffany Fougeray 1Arnaud Polizzi 2Marion Régnier 2Anne Fougerat 2Sandrine Ellero-Simatos 2Yannick Lippi 2Sarra Smati 3Frédéric Lasserre 2Blandine Tramunt 4Marine Huillet 2Léonie Dopavogui 2Juliette Salvi 5Emmanuelle Nédélec 5Vincent Gigot 5Lorraine Smith 2Claire Naylies 2Caroline Sommer 2Joel T Haas 6Walter Wahli 7Hélène Duez 6Pierre Gourdy 4Laurence Gamet-Payrastre 2Alexandre Benani 5Anne-Françoise Burnol 8Nicolas Loiseau 2Catherine Postic 8Alexandra Montagner 9Hervé Guillou 10Affiliations expand

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Liver physiology is circadian and sensitive to feeding and insulin. Food intake regulates insulin secretion and is a dominant signal for the liver clock. However, how much insulin contributes to the effect of feeding on the liver clock and rhythmic gene expression remains to be investigated. Insulin action partly depends on changes in insulin receptor (IR)-dependent gene expression. Here, we use hepatocyte-restricted gene deletion of IR to evaluate its role in the regulation and oscillation of gene expression as well as in the programming of the circadian clock in the adult mouse liver. We find that, in the absence of IR, the rhythmicity of core-clock gene expression is altered in response to day-restricted feeding. This change in core-clock gene expression is associated with defective reprogramming of liver gene expression. Our data show that an intact hepatocyte insulin receptor is required to program the liver clock and associated rhythmic gene expression.

Keywords: CLOCK; CP: Metabolism; CP: Molecular biology; circadian; hepatocyte; insulin; insulin receptor; liver; metabolism.