Melatonin Receptor 1 Deficiency Affects Feeding Dynamics and Pro-Opiomelanocortin<b> </b>Expression in the Arcuate Nucleus and Pituitary of Mice

Abstract

Background/Methods: Melatonin, the neurohormone for darkness, mediates photoperiod-dependent changes in physiology and behavior by targeting specific membrane-bound receptors (MT1 and MT2). In the present study, we investigated the impact of MT1 receptor deficiency on feeding behavior, locomotor activity and mRNA expression levels encoding for the polypeptide pro-opiomelanocortin (Pomc) and neuropeptide Y (Npy) in the hypothalamic arcuate nucleus (ARC) and the adenohypophysis [pars distalis (PD) and pars intermedia (PI)] in a comparison between wild-type (WT) and MT1-deficient (MT1-/-) mice. Results: The MT1-/- mice spent significantly more time feeding than the WT mice, while the general locomotor behavior, body weight and the total amount of food consumed did not differ between both genotypes. The nocturnal expression levels of Pomc in the ARC and PD were significantly higher in WT as compared to MT1-/- mice and exogenous melatonin administered during the light phase stimulated Pomc expression in WT mice only. No differences were found between WT and MT1-/- mice with regard to Pomc expression levels in the PI. Conclusion: Thus, the MT1-mediated signaling stimulates Pomc expression in a region-specific pattern. Since the MT1-mediated changes in Pomc expression do not elicit direct orexigenic or anorexigenic effects, such effects are obviously mediated by regulatory systems downstream of the Pomc mRNA (e.g. cleavage and release of POMC derivatives), which are independent of MT1 signaling.

Seasonal consumption of polyphenol-rich fruits affects the hypothalamic leptin signaling system in a photoperiod-dependent mode

“…Nevertheless, cherries are also rich on melatonin 48 , a hormone that provides information about day length, controlling seasonal phenotypic adjustments 49 . Interestingly, melatonin reduces the energy expenditure induced by cold exposure in the Siberian hamster placed at LD 50 and stimulates Pomc expression in mice 51 . Therefore, the melatonin contained in cherries could significantly contribute to the metabolic effects induced by cherry intake observed in this study.…”

Melatonin prevents early pituitary dysfunction induced by sucrose‐rich diets

“…Nonetheless, Jusczak et al showed that intracerebroventricular infusion of melatonin resulted in a significant decrease in rat plasma ACTH levels that could not be blocked by receptor antagonists (luzindole or 4‐phenyl‐2‐propionamidotetralin). Notwithstanding, Fischer et al demonstrated that an acute treatment with melatonin (2.5 hours) in mice stimulated POMC expression in the pituitary pars distalis , an effect that was not observed in MT1 −/− mice . Altogether, melatonin could affect HPA axis activity by exerting direct effects on pituitary pars distalis (receptor‐independent) by interacting with MT1/MT2 receptors, by other mechanisms (eg, free radical scavenger, interaction with orphan nuclear receptors and molecules, as calmodulin) or by a combination of some or all the above.…”

“…Notwithstanding, Fischer et al demonstrated that an acute treatment with melatonin (2.5 hours) in mice stimulated POMC expression in the pituitary pars distalis, an effect that was not observed in MT1 −/− mice. 89 Altogether, melatonin could affect HPA axis activity by exerting direct effects on pituitary pars distalis (receptor-independent) by interacting with MT1/MT2 receptors, by other mechanisms (eg, free radical scavenger, interaction with orphan nuclear receptors and molecules, as calmodulin) or by a combination of some or all the above. The complexity of the processes involved makes it difficult to determine the precise contribution of each mechanism to the effect of melatonin on the HPA axis activity.…”

Melatonin potentiates the effects of metformin on glucose metabolism and food intake in high‐fat‐fed rats

“…38 Moreover, exogenous melatonin in rats leads to overall reduced food intake, due to smaller and shorter meals. In particular, mice KO for MT1 spend more time feeding.…”

“…In particular, mice KO for MT1 spend more time feeding. 38 Moreover, exogenous melatonin in rats leads to overall reduced food intake, due to smaller and shorter meals. 18…”