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Journal of Biochemistry Advance Access published online on January 27, 2009
Journal of Biochemistry, doi:10.1093/jb/mvp018
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© The authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Gender Disparity of Hepatic Lipid Homeostasis Regulated by the Circadian Clock

Xiaoxia Yang, Yu-Kun Jennifer Zhang, Noriko Esterly, Curtis D. Klaassen and Yu-Jui Yvonne Wan

Department of Pharmacology, Toxicology & Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160 U.S.A.

To Whom Correspondence Should Be Sent: Yu-Jui Yvonne Wan, Ph.D., Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 4059 Kansas Life Sciences Innovation Center (KLSIC), 3901 Rainbow Blvd, Kansas City, KS 66160, Tel.: 913-588-9111; Fax: 913-588-7501, E-mail: ywan{at}kumc.edu

Received October 22, 2008; Accepted January 17, 2009


  Abstract

The mammalian clock regulates major aspects of energy metabolism including glucose and lipid homeostasis as well as mitochondrial oxidative metabolism. This study is to identify specific patterns of circadian rhythms for lipid homeostasis in both female and male mouse livers, and to clarify gender disparity in coupling the peripheral circadian clock to lipid metabolic outputs by nuclear receptors. To achieve this, profiling the diurnal hepatic expression of genes encoding circadian clocks, nuclear receptors, and lipid metabolic enzymes was performed. Hepatic lipid levels including cholesterol, triglyceride, and nonesterified fatty acids (NEFA) were monitored over a 24-hr period. The Cosinor analysis revealed that several genes encoding nuclear receptors and enzymes involved in the lipid metabolic pathway were rhythmically expressed in liver in phase with the peripheral clocks, which were correlated with the diurnal changes of hepatic lipid levels. Gender disparity was observed for circadian characteristics including mesor and amplitude values, accompanied with advances in acrophases in female mouse livers. Accordingly, gender differences were also observed in diurnal lipid homeostasis. The identification of cycling patterns for lipid metabolic pathways in both female and male mouse livers may shed light on the development of gender-based treatment for human diseases related to the coordination of the cellular clock and control of lipid homeostasis.

Key Words: Circadian rhythm, gender, lipid homeostasis, liver, nuclear receptor


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