www.impactaging.com

AGING, February 2009, Vol. 2. No 2 Research Perspective

Circadian clock‐coordinated hepatic lipid metabolism: only transcriptional regulation? Frédéric Gachon1, Xavier Bonnefont2 1 Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, CH‐1005, Switzerland 2 CNRS, UMR 5203, Institut de Génomique Fonctionnelle, 34094 Montpellier, France
Running title: Rhythmic post‐transcriptional regulation of lipid metabolism Key words: Circadian clock, Lipid metabolism, Unfolded protein response, IRE1α, autophagy, growth hormone Correspondence: Frédéric Gachon, PhD, Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Rue du Bugnon, 27, CH‐1005, Switzerland Received: 02/09/10; accepted: 02/16/10; published on line: 02/17/10 E‐mail: Frederic.Gachon@unil.ch Copyright: © Gachon and Bonnefont. This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Abstract: By regulating the metabolism of fatty acids, carbohydrates, and xenobiotic, the mammalian circadian clock plays a fundamental role on the liver physiology. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. However, recent evidences suggest that some signaling pathways synchronized by the circadian clock can also influence metabolism at a post‐transcriptional level. In this context, we have recently shown that the circadian clock synchronizes the rhythmic activation of the IRE1α pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock, provokes deregulation of endoplasmic reticulum‐localized enzymes, and leads to impaired lipid