Journal of Biochemistry Advance Access originally published online on January 27, 2009
Journal of Biochemistry 2009 145(5):609-623; doi:10.1093/jb/mvp018
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Gender Disparity of Hepatic Lipid Homoeostasis Regulated by the Circadian Clock
Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, USA
*To whom correspondence should be addressed. Tel: +1 913 588 9111, Fax: +1 913 588 7501, E-mail: ywan{at}kumc.edu
Received October 22, 2008; Accepted January 17, 2009
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Abstract |
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The mammalian clock regulates major aspects of energy metabolism, including glucose and lipid homoeostasis as well as mitochondrial oxidative metabolism. This study is to identify specific patterns of circadian rhythms for lipid homoeostasis 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 non-esterified fatty acids (NEFAs) were monitored over a 24-h 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 homoeostasis. 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 homoeostasis.
Key Words: Circadian rhythm, gender, lipid homoeostasis, liver, nuclear receptor
Abbreviations:
Bmal1, brain and muscle Arnt-like protein 1; Clock, circadian locomotor output cycles kaput; Cry, cryptochrome; LXR, liver X receptor; Mesor, midline estimating statistic of rhythm; NEFA, non-esterified fatty acids; Per, period; PGC1, PPAR
coactivator 1; PPAR, peroxisome proliferator-activated receptor; ROR, retinoid-related orphan receptor; RORE, ROR response element
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