Circadian expression of genes regulating food intake

Objective: The Agouti-related protein (AgRP), neuropeptide Y (NPY), proopiomelanocortin (POMC), cocaine and amphetamine-regulated transcript (CART), Orexin, melanin concentrating hormone (MCH), leptin, and its hypothalamic receptor (LR) are key regulators of food intake and energy homeostasis. In the present study, we examined the circadian expression profiles of these genes. Research Methods and Procedures: We used quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to measure mRNA levels, spectral analysis to evaluate periodicity, and correlation analysis to examine for associations with diurnal food intake. Results: No gene in particular stood out as a strong candidate, but the overall circadian expression profiles of leptin and its hypothalamic receptor came close to statistically and graphically resembling the diurnal feeding behavior of mice. In mathematical terms, adrenal AgRP exhibited strong circadian expression and had the highest correlation with food intake, followed by leptin. Yet its highest point of expression occurred 8 hours after nocturnal food intake had peaked, suggesting that adrenal AgRP could not play a direct role in the initiation of nocturnal feeding; neither did hypothalamic AgRP, NPY, POMC, CART, Orexin, or MCH. Discussion: These data show that ad libitum feeding in mice is influenced by complex central and peripheral circuits involving orexigenic and anorectic agents of which leptin and its hypothalamic receptor could play more prevalent roles.