Evidence that alpha-calcitonin gene-related peptide is a neurohormone that controls systemic lipid availability and utilization.
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.
Danaher
Rachel N
RN
School of Biological Sciences, University of Auckland, Private Bag 92 019, Auckland, New Zealand.
Loomes
Kerry M
KM
Leonard
Bridget L
BL
Whiting
Lynda
L
Hay
Debbie L
DL
Xu
Lance Yi
LY
Kraegen
Edward W
EW
Phillips
Anthony R J
AR
Cooper
Garth J S
GJ
D055372:AMP-Activated Protein Kinases; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis; D050356:Lipid Metabolism / Q000187:drug effects*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000502:physiology
D005227:Fatty Acids; D009097:Multienzyme Complexes; D018377:Neurotransmitter Agents; D018015:Receptors, Calcitonin Gene-Related Peptide; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D015740:Calcitonin Gene-Related Peptide