Effect of melanocortin-1 receptor in the regulation of beta3-adrenoceptor agonist-induced BAT thermogenesis
Khadka, Rapson (2019-03-01)
Julkaisun pysyvä osoite on:
Adipose tissue is comprised of brown and white adipose tissues. In particular, brown adipose tissues (BAT) or brown fat contain rich amount of beta3-adrenoceptors (β3AR) and they are regulated by sympathetic nervous system (SNS). Indeed, BAT contains unique protein called uncoupling protein 1 (UCP1) that causes non-shivering thermogenesis via mitochondrial uncoupling of oxidative phosphorylation respiratory chain. Central melanocortin system (CMS) that involves melanocortin-3 and melanocortin-4 receptors regulates energy intake and energy expenditure (EE). CMSmediated EE occurs through the involvement of BAT. It is known that defective CMS signaling produces obese phenotype because of altered CMS action in EE. Preliminary work from my research group has found the similar kind of EE alteration and obese characteristics in melanocortin-1 receptor deficient (MC1Re/e) mice. The aim of the present experiment centers on finding if this defective EE in MC1Re/e mice is occurring via BAT thermogenesis. Using mutant yellow MC1Re/e mice and wild type C57BL/6 mice, β3AR agonist CL-316243 was administered intraperitoneally to induce BAT thermogenesis. Infrared thermography (IRT) technique was used to measure the temperatures of interscapular area overlying BAT and lower body (LB) area that is devoid of BAT. Results showed no significant difference between WT and MC1Re/e mice in terms of induced BAT temperature increment suggesting that defective MC1R responsible for reduced EE and increased adiposity is not associated with BAT thermogenic activity. However, small notable variance in temperature difference of BAT and LB between the genotypes implicated the possible role of MC1R in BAT-originated heat transmission across the body via impaired vasodilatation.