Mice Lacking the Neuropeptide Alpha-Calcitonin Gene-Related Peptide Are Protected Against Diet-Induced Obesity

Endocrinology. 2010 Sep;151(9):4257-69. doi: 10.1210/en.2010-0284. Epub 2010 Jul 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Acetyl-CoA Carboxylase / metabolism
  • Adiposity / physiology
  • Animals
  • Blotting, Western
  • Body Temperature / physiology*
  • Body Weight / physiology
  • Calcitonin Gene-Related Peptide / deficiency
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / physiology*
  • Citrate (si)-Synthase / metabolism
  • DNA, Mitochondrial / genetics
  • Dietary Fats / administration & dosage
  • Dietary Fats / adverse effects*
  • Energy Metabolism / physiology
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Fatty Liver / physiopathology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondrial Proteins / metabolism
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / physiopathology*
  • Oxygen Consumption / physiology
  • Triglycerides / metabolism

Substances

  • DNA, Mitochondrial
  • Dietary Fats
  • Mitochondrial Proteins
  • Triglycerides
  • Citrate (si)-Synthase
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase
  • Calcitonin Gene-Related Peptide