Neuroanatomy of melanocortin-4 receptor pathway in the mouse brain

OBJECTIVE: Melanocortin-4 receptors (MC4Rs) are key regulators of energy homeostasis and adipose deposition in the central nervous system. Considering that MC4R expression regions and function-related research mainly focus on the paraventricular nucleus (PVN), little is known about their distribution throughout the mouse brain, although its messenger RNA distribution has been analyzed in the rat. Therefore, MC4R protein localization in mouse neurons was the focus of this study. METHODS: MC4R protein distribution was assessed in mice through immunofluorescence and Western blotting. RESULTS: MC4R was differentially expressed throughout the arcuate nucleus (ARC), nucleus of the solitary tract (NTS), raphe pallidus (RPa), medial cerebellar nucleus, intermediolateral nucleus, and brainstem. The highest MC4R protein levels were found in the ARC and ventromedial hypothalamic nucleus, while they were significantly lower in the parabrachial nucleus and NTS. The lowest MC4R protein levels were found in the PVN; there was no difference in the protein levels between the area postrema and RPa. CONCLUSIONS: These data provide a basic characterization of MC4R-expressing neurons and protein distribution in the mouse brain and may aid further research on its role in energy homeostasis.