Activity of the Hypothalamic Melanocortin System Decreases in Middle-Aged and Increases in Old Rats

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2018-03, Vol.73 (4), p.438-445
• Main Authors: Füredi, Nóra, Mikó, Alexandra, Gaszner, Balázs, Feller, Diána, Rostás, Ildikó, Tenk, Judit, Solymár, Margit, Balaskó, Márta, Pétervári, Erika
• Format: Article
• Language: English
• Subjects: Age Factors; Aging; Agouti-Related Protein - metabolism; alpha-MSH - pharmacology; Animals; Anorexia; Anorexia - metabolism; Arcuate Nucleus of Hypothalamus - metabolism; Body composition; Body Weight; Calorimetry, Indirect; Eating - drug effects; Fluorescent Antibody Technique; Gene Expression; Hypothalamus; Immunohistochemistry; Male; Melanocortin; Melanocortins - metabolism; Microscopy, Confocal; Models, Animal; Obesity; Obesity - metabolism; Oxygen Consumption; Paraventricular Hypothalamic Nucleus - metabolism; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Rodents
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/glx213

Appearance of middle-aged obesity and aging anorexia both in humans and rodents suggests a role for regulatory alterations. Hypothalamic melanocortin agonist, α-melanocyte-stimulating hormone (α-MSH) produced in the arcuate nucleus (ARC), reduces body weight via inducing hypermetabolism and anorexia mainly through melanocortin 4 receptors (MC4Rs) in the paraventricular nucleus (PVN). Orexigenic ARC-derived agouti-related protein (AgRP) is an inverse agonist on MC4R in the PVN. Previously, we demonstrated that characteristic age-related shifts in the catabolic effects of α-MSH may contribute both to middle-aged obesity and aging anorexia. Responsiveness to α-MSH decreases in middle-aged rats compared with young adults, whereas in old age it rises again significantly. We hypothesized corresponding age-related dynamics of endogenous melanocortins. Therefore, we quantified mRNA gene expression and peptide or protein level of α-MSH, AgRP, and MC4R in the ARC and PVN of male Wistar rats of five age groups (from young to old). Immunofluorescence and quantitative reverse transcriptase polymerase chain reaction were applied. α-MSH and MC4R immunoreactivities in the ARC and PVN declined in middle-aged and increased together with their expressions in aging rats. AgRP gene expression but not its immunoreactivity increased in aging rats. Our results demonstrate that age-dependent changes of endogenous melanocortins contribute to middle-aged obesity and aging anorexia.