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Publication : Mice lacking the neuropeptide alpha-calcitonin gene-related peptide are protected against diet-induced obesity.

First Author  Walker CS Year  2010
Journal  Endocrinology Volume  151
Issue  9 Pages  4257-69
PubMed ID  20610563 Mgi Jnum  J:169504
Mgi Id  MGI:4941119 Doi  10.1210/en.2010-0284
Citation  Walker CS, et al. (2010) Mice lacking the neuropeptide alpha-calcitonin gene-related peptide are protected against diet-induced obesity. Endocrinology 151(9):4257-69
abstractText  Alpha-calcitonin gene-related peptide (alphaCGRP) is a neuropeptide that is expressed in motor and sensory 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 alphaCGRP in lipid metabolism by chronically challenging alphaCGRP-specific knockout (alphaCGRP(-/-)) 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, alphaCGRP(-/-) 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, alphaCGRP(-/-) 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. AlphaCGRP(-/-) 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 alphaCGRP as a mediator of energy metabolism and opens up therapeutic opportunities to target CGRP action in obesity.
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