Circadian Expression of Genes Regulating Food Intake

Abstract

(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.

Possible Involvement of Hypothalamic Nucleobindin-2 in Hyperphagic Feeding in Tsumura Suzuki Obese Diabetes Mice

“…Nocturnal rodents such as mice and rats feed primarily during the dark hours, and characteristically eat their largest meal shortly after onset of the dark phase. 54) NPY signaling is required for a circadian cue to increase food intake. 55) NPY synthesis in the hypothalamus is enhanced before the onset of the dark phase; i.e., a relatively high level of NPY mRNA is detected approximately 4 h before the onset of the dark phase in the hypothalamus of mice and rats.…”

Diurnal variation of the melanin-concentrating hormone level in the hypothalamus

“…Harthoorn et al [9] selected 25 MCH neurons in the rat hypothalamus and found that their MCH content did not depend on the diurnal time point. Likewise, the expression profile of the Pmch gene did not exhibit particularly strong circadian expression profile in mice [20], similarly to several other genes regulating food intake. Dias Abdo Agamme et al [6] also observed absence of day/night differences in Pmch expression in the rat hypothalamus under undisturbed conditions.…”

“…To address this issue, the possible diurnal variation of the MCH level in the various target areas should be studied as well. As far as the replenishment of the pool is concerned, earlier results indicated that the level of Pmch gene expression, as characterized by the MCH mRNA level, does not depend on the time of the day [6,20]. It is to be considered, that beyond transcription, formation of mature MCH involves translation of the mRNA to preproMCH and the posttranslational proteolytic cleavage of the emerging prohormone [15,23] as well.…”

“…ZT0 traditionally corresponds to turning the lights on.) Similarly, statistically significant correlations were not found between the periodic expression of MCH and orexin genes with food intake in mouse hypothalamus [20].…”

Circadian rhythms and clocks in adipose tissues: current insights

“…For example, leptin transport into the brain and the mRNA expression of its receptor, LepR (or ObR), show diurnal rhythmicity in the hypothalamus. 129,130 This could indicate circadian rhythms in the central sensitivity to leptin and interpretation of the leptin signal (circadian gating). Indeed, destruction of LepR-expressing neurons in the arcuate nucleus leads to dampened feeding rhythms and to arrhythmicity of locomotor activity in DD.…”