High-fat Intake is Associated with Alteration of Peripheral Circadian Clock Gene Expression

ABSTRACT

PURPOSE: Recent studies demonstrated disruption of the circadian clock gene is associated with the development of obesity and metabolic syndrome. Obesity is often caused by the high calorie intake, In addition, the chronic stress tends to contribute to the increased risk for obesity. To evaluate the molecular mechanisms, we examined the expression of circadian clock genes in high fat diet-induced mice models with the chronic stress. METHODS: C57BL/6J mice were fed with a 45% or 60% high fat diet for 8 weeks. Daily immobilization stress was applied to mice fed with a 45% high fat for 16 weeks. We compared body weight, food consumption, hormone levels and metabolic variables in blood. mRNA expression levels of metabolic and circadian clock genes in both fat and liver were determined by quantitative RT-PCR. RESULTS: The higher fat content induced more severe hyperglycemia, hyperlipidemia and hyperinsulinemia, and these results correlated with their relevant gene expressions in fat and liver tissues. Chronic stress had only minimal effects on metabolic variables, but it altered the expression patterns of metabolic and circadian clock genes. These results suggest that the fat metabolism regulates the function of the circadian clock genes in peripheral tissues, and stress hormones may contribute to its regulation.