Regulation of hepatic metabolism: the role of the P16 regulator demonstrated

CDKN2A/p16INK4a suppresses hepatic fatty acid oxidation through the AMPKα2-SIRT1-PPARα signaling pathway.   
Yann Deleye, Alexia Karen Cotte, Sarah Anissa Hannou, Nathalie Hennuyer, Lucie Bernard  , Bruno Derudas, Sandrine Caron, Vanessa Legry, Emmanuelle Vallez, Emilie Dorchies, Nathalie Martin, Steve Lancel, Jean-Sébastien Annicotte, Kadiombo Bantubungi, Albin Pourtier, Violeta Raverdy, François Pattou, Philippe Lefebvre, Corinne Abbadie, Bart Staels, Joel T Haas, Réjane Peaumelle.
J Biol Chem. 2020 Oct 9;jbc.RA120.012543.

Cell cycle regulators are widely studied in cancer and aging. Pr Réjane Paumelle’s team at the Institut Pasteur de Lille (U1011-EGID) has shown that some of these regulators, such as p16INK4a (p16), can also play a role in the regulation of hepatic metabolism independently of their role in the cell cycle control. Using a mouse or hepatocyte model deficient for p16 expression, the team showed that p16 was important in controlling lipid metabolism during fasting and the development of hepatic steatosis by a mechanism dependent on the nuclear receptor PPARalpha.

This work confirms previous work showing a genetic link between mutations close to the p16 / CDKN2A locus and certain metabolic disorders such as type 2 diabetes and cardiovascular diseases. Thus, by decreasing the expression of p16, it might be possible to preserve hepatic metabolic flexibility and reduce the development of these pathologies.

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