Endogenous Calcitonin Gene-Related Peptide Regulates Lipid Metabolism and Energy Homeostasis in Male Mice.
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP-specific knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice. Fatty liver changes were less severe in CGRP-/- mice, which also showed lower serum insulin and leptin levels. Glucose tolerance and insulin sensitivity were better in CGRP-/- than WT mice, and expired gas analysis revealed greater oxygen consumption by CGRP-/- mice. Adipocyte hypertrophy was suppressed in CGRP-/- mice, while expression of β-3-adrenergic receptor, hormone-sensitive lipase and adiponectin was enhanced. Isoproterenol-induced glycerol release from WAT was higher in CGRP-/- than WT mice, and CGRP-/- mice showed elevated sympathetic nervous activity. β-receptor-blockade canceled the beneficial effects of CGRP deletion on obesity. These results suggest that, in addition to its actions in the cardiovascular system, endogenous CGRP is a key regulator of metabolism and energy homeostasis in vivo.
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Tian
T
Liu
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Akiko
A
Kamiyoshi
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Takayuki
T
Sakurai
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Yuka
Y
Ichikawa-Shindo
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Hisaka
H
Kawate
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Lei
L
Yang
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Megumu
M
Tanaka
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Xian
X
Xian
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Akira
A
Imai
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Liuyu
L
Zhai
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Kazutaka
K
Hirabayashi
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Kun
K
Dai
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Keiya
K
Tanimura
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Teng
T
Liu
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Nanqi
N
Cui
Japan Bio Products Co., Ltd., Tokyo 151-0063, Japan.
Kyoko
K
Igarashi
Japan Bio Products Co., Ltd., Tokyo 151-0063, Japan.
Akihiro
A
Yamauchi
Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano 390-8621, Japan.
Takayuki
T
Shindo
D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena / Q000235:genetics; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010101:Oxygen Consumption / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D005947:Glucose; D015740:Calcitonin Gene-Related Peptide