Mice lacking the neuropeptide alpha-calcitonin gene-related peptide are protected against diet-induced obesity.
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.
Walker
Christopher S
CS
School of Biological Sciences, University of Auckland, Private Bag 92 019, Auckland 1142, New Zealand.
Li
Xiaoling
X
Whiting
Lynda
L
Glyn-Jones
Sarah
S
Zhang
Shaoping
S
Hickey
Anthony J
AJ
Sewell
Mary A
MA
Ruggiero
Katya
K
Phillips
Anthony R J
AR
Kraegen
Edward W
EW
Hay
Debbie L
DL
Cooper
Garth J S
GJ
Loomes
Kerry M
KM
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D050154:Adiposity / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004734:Energy Metabolism / Q000502:physiology; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D010101:Oxygen Consumption / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
D004272:DNA, Mitochondrial; D004041:Dietary Fats; D024101:Mitochondrial Proteins; D014280:Triglycerides; D002950:Citrate (si)-Synthase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D015740:Calcitonin Gene-Related Peptide