Stimulation of melanocortin-3 receptors accelerates the satiation process and increases the α-MSH expression in high-fat diet-fed rats.

Abstract

The knowledge about the role of MC3 receptors (MC3r) in the regulation of feeding behavior is limited. The present study was conducted to determine whether MC3r mediates the hypophagic effects of the melanocortins under conditions of positive energy balance. Male Wistar rats were fed with a high-fat diet (HFD) for 15 days and on day 16 the animals received an intracerebroventricular injection of the following treatments: Vehicle, D-Trp8-γ-melanocyte-stimulating hormone (MSH; MC3r agonist), SHU9119 (MC3r/MC4r antagonist), or D-Trp8-γ-MSH+SHU9119. Food intake was measured and the behavioral satiety sequence (BSS) analysis was carried out during the first hour of the dark phase. The c-Fos and α-MSH immunoreactivity in the arcuate nucleus (ARC) was evaluated 60 min later the onset of food intake. The results indicated that D-Trp8-γ-MSH decreased the ingestion of the HFD and this effect is associated with the early development of the satiation process Moreover, the D-Trp8-γ-MSH increased the accumulation of the α-MSH in the ARC and the c-Fos activity in the PVN. The antagonist SHU9119 partially prevented the D-Trp8-γ-MSH-induced hypophagia. Moreover, behavioral analysis suggests that central activation of MC3r accelerated the cessation of feeding in conditions of positive energy balance; the possible role of MC4r is discussed. Present data indicate that central stimulation of MC3r prevented the overconsumption of the HFD without affecting the natural satiation process, suggesting a potential use of MC3r for the treatment of eating disorders that are stimulated by hypercaloric diets.

Melanocortinas y su participación en el desarrollo de la obesidad

“…La hiperfagia se ha asociado con la inhibición de las neuronas POMC del ARC, debido a que los rMC3 actúan como autoreceptores inhibitorios (Marks et al, 2006). En tanto que la hipofagia podría estar mediada por la síntesis de la α-MSH y posiblemente por la consecuente estimulación de los rMC4 (Díaz-Urbina et al, 2021). El funcionamiento anormal del receptor MC3 se ha asociado con una mayor acumulación de tejido adiposo (cabe mencionar que la obesidad de forma general es definida como una acumulación anormal o excesiva de grasa), además de patrones conductuales asociados con conductas compulsivas de alimentación.…”