Evidence that alpha-calcitonin gene-related peptide is a neurohormone that controls systemic lipid availability and utilization.

Abstract:

:Alpha-calcitonin gene-related peptide (alphaCGRP) is released mainly from sensory and motor nerves in response to physiological stimuli. Despite well-documented pharmacological effects, its primary physiological role has thus far remained obscure. Increased lipid content, particularly in skeletal muscle and liver, is strongly implicated in the pathogenesis of insulin resistance, but the physiological regulation of organ lipid is imperfectly understood. Here we report our systematic investigations of the effects of alphaCGRP on in vitro and in vivo indices of lipid metabolism. In rodents, levels of alphaCGRP similar to those in the blood markedly stimulated fatty acid beta-oxidation and evoked concomitant mobilization of muscle lipid via receptor-mediated activation of muscle lipolysis. alphaCGRP exerted potent in vivo effects on lipid metabolism in muscle, liver, and the blood via receptor-mediated pathways. Studies with receptor antagonists were consistent with tonic regulation of lipid metabolism by an endogenous CGRP agonist. These data reveal that alphaCGRP is a newly recognized regulator of lipid availability and utilization in key tissues and that it may elevate the availability of intramyocellular free fatty acids to meet muscle energy requirements generated by contraction by evoking their release from endogenous triglyceride.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Danaher RN,Loomes KM,Leonard BL,Whiting L,Hay DL,Xu LY,Kraegen EW,Phillips AR,Cooper GJ

doi

10.1210/en.2007-0583

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

154-60

issue

1

eissn

0013-7227

issn

1945-7170

pii

en.2007-0583

journal_volume

149

pub_type

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