Abstract:
alpha-Calcitonin gene-related peptide ({alpha}CGRP) is a neuropeptide that is expressed inmotorandsensory neurons. It is a powerful vasodilator and has been implicated in diverse metabolic roles. However, its precise physiological function remains unclear. In this study, we investigated the role of {alpha}CGRP in lipid metabolism by chronically challenging {alpha}CGRP-specific knockout ({alpha}CGRP^{-/-}) and control mice with high-fat diet regimens. At the start of the study, both animal groups displayed similar body weights, serum lipid markers, and insulin sensitivity. However, ({alpha}CGRP^{-/-}) mice displayed higher core temperatures, increased energy expenditures, and a relative daytime (nonactive) depression in respiratory quotients, which indicated increased beta-oxidation. In response to fat feeding, ({alpha}CGRP^{-/-}) mice were comparatively protected against diet-induced obesity with an attenuated body weight gain and an overall reduction in adiposity across all the three diets examined. ({alpha}CGRP^{-/-}) mice also displayed improved glucose handling and insulin sensitivity, lower im and hepatic lipid accumulation, and improved overall metabolic health. These findings define a new role for {alpha}CGRP as a mediator of energy metabolism and opens up therapeutic opportunities to target CGRP action in obesity.
