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  • Title: Activity of the Hypothalamic Melanocortin System Decreases in Middle-Aged and Increases in Old Rats.
    Author: Füredi N, Mikó A, Gaszner B, Feller D, Rostás I, Tenk J, Solymár M, Balaskó M, Pétervári E.
    Journal: J Gerontol A Biol Sci Med Sci; 2018 Mar 14; 73(4):438-445. PubMed ID: 29099963.
    Abstract:
    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.
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