Abnormal expressions of circadian-clock and circadian clock-controlled genes in the livers and kidneys of long-term, high-fat-diet-treated mice

Objectives: Physiological and behavioral circadian rhythmicities are exhibited by all mammals and are generated by intracellular levels of circadian oscillators, which are composed of transcriptional/translational feedback loops involving a set of circadian-clock genes, such as Clock, Per1-3, Cry1-2, Bmal1, Dbp, E4BP4 and CK1 epsilon. These circadian-clock genes play important roles in regulating circadian rhythms and also energy homeostasis and metabolism. Determining whether obesity induced by high-fat diet affected the expressions of circadian-clock genes and their related genes in peripheral tissues, was the main focus of this study. To address this issue, we fed male C57BL/6 mice a high-fat diet for 11 months to induce obesity, hyperglycemic, hypercholesterolemic and hyperinsulinemic symptoms, and used quantitative real-time reverse transcription-PCR to measure gene expression levels. Results: We found that the expressions of circadian-clock genes and circadian clock-controlled genes, including Per1-3, Cry1-2, Bmal1, Dbp, E4BP4, CK1 epsilon, PEPCK, PDK4 and NHE3, were altered in the livers and/or kidneys. Conclusions: These results indicate that obesity induced by high-fat diet alters the circadian-clock system, and obesity and metabolic syndrome are highly correlated with the expressions of circadian-clock genes and their downstream, circadian clock-controlled genes. International Journal of Obesity ( 2010) 34, 227-239; doi: 10.1038/ijo.2009.228; published online 10 November 2009