Anti-PYY polyclonal antibody

Central melanocortin 4 receptors (MC4Rs) stimulate energy expenditure and inhibit food intake. MC4Rs activate the G protein G(s), but whether G(s) mediates all MC4R actions has not been established. Individuals with Albright hereditary osteodystrophy (AHO), who have heterozygous G(s)-inactivating mutations, only develop obesity when the G(s) mutation is present on the maternal allele because of tissue-specific genomic imprinting. Furthermore, evidence in mice implicates G(s) imprinting within the central nervous system (CNS) in this disorder. In this study, we examined the effects of G(s) in MC4R-expressing cells on metabolic regulation. Mice with homozygous G(s) deficiency in MC4R-expressing cells (MC4RGsKO) developed significant obesity with increased food intake and decreased energy expenditure, along with impaired insulin sensitivity and cold-induced thermogenesis. Moreover, the ability of the MC4R agonist melanotan-II (MTII) to stimulate energy expenditure and to inhibit food intake was impaired in MC4RGsKO mice. MTII failed to stimulate the secretion of the anorexigenic hormone peptide YY (PYY) from enteroendocrine L cells, a physiological response mediated by MC4R-G(s) signaling, even though baseline PYY levels were elevated in these mice. In G(s) heterozygotes, mild obesity and reduced energy expenditure were present only in mice with a G(s) deletion on the maternal allele in MC4R-expressing cells, whereas food intake was unaffected. These results demonstrate that G(s) signaling in MC4R-expressing cells is required for controlling energy balance, thermogenesis, and peripheral glucose metabolism. They further indicate that G(s) imprinting in MC4R-expressing cells contributes to obesity in G(s) knockout mice and probably in individuals with Albright hereditary osteodystrophy as well.

Background & aim Changes in eating behavior occur in the elderly due to oral and swallowing dysfunctions. We aimed to clarify the difference between basal meal patterns of young and aged mice in relation to appetite regulating hormones. Methods: Thirty two of young (7-week-old) and aged (23-25-month-old) C57BL/6 male mice were acclimated to a single housing and then transferred to a highly sensitive automated feeding monitoring device. Feeding behavior was monitored from the onset of the dark phase after habituation to the device. Plasma peptide YY (PYY) levels were assessed under the several feeding status or after treatment of PYY. PYY and its receptor (NPY Y2 receptor, Y2R) antagonist were intraperitoneally administered 30 min before the monitoring. Results: Although the basal 24-h meal amounts did not differ by age, the total meal time and frequency of minimum feeding activity (bout) were significantly increased and the average bout size and time per bout were significantly decreased in aged mice. PYY dynamics were abnormal and the temporal reduction in food intake by exogenous PYY was more prominent in aged mice than in young mice. PYY administration to young mice induced aged-like meal patterns, and Y2R antagonist administration to aged mice induced young-like meal patterns. Conclusions: Aged mice exhibited characteristic meal patterns probably due to PYY metabolism dysfunction and/or enhanced PYY-Y2R signaling, suggesting a novel method for assessing eating difficulties in aged animals and a potential target for the remedy.