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Gender disparity of hepatic lipid homeostasis regulated by the circadian clock

The current 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 peripheral circadian clock to lipid metabolic outputs by nuclear receptors. 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 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 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 genders may shed light on the development of gender‐based treatment for human diseases related to the coordination of cellular clock and control of lipid homeostasis. This work is supported by grants from National Institutes of Health [CA53596, AA14147] and COBRE [P20 RR021940].