The approach to the mechanism of calcitonin gene-related peptide-inducing inhibition of food intake.
The aim of this study was to investigate the anorectic mechanism of calcitonin gene-related peptide (CGRP) in rats. Intraperitoneal injection of CGRP (50 μg/kg) resulted in decline (p < 0.05) in the food intake of rats at 0.5, 1, 2 and 4 h in comparison with saline control. Compared with saline-treated group, the levels of hypothalamic 3',5'-cyclic adenosine monophosphate (cAMP) and plasma glucagon were increased (p < 0.05) in CGRP-treated group, but insulin level was decreased (p < 0.05). No significant changes (p > 0.05) in the plasma leptin were observed between two treatment groups. Calcitonin gene-related peptide injection down regulated (p < 0.05) both neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) genes at mRNA levels, but up regulated (p < 0.05) the expression of cholecystokinin (CCK) gene. The correlations analysis showed that food intake was negatively correlated (p < 0.05) with CCK mRNA, cAMP and glucagon levels. Moreover, there existed negative correlations (p < 0.05) between MCH mRNA and glucagon levels, and positive correlations (p < 0.05) between insulin and leptin levels. The results showed that cAMP acting as the second messenger may play a vital role in the anorectic effects of CGRP. Calcitonin gene-related peptide could stimulate anorexigenic neuropeptides (i.e. CCK) and/or inhibit orexigenic neuropeptides (i.e. NPY and MCH) expression, and ultimately suppressed food intake that was functionally coupled to cAMP/PKA pathway activation.
Sun
J-Y
JY
The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou, China. jysun@zju.edu.cn
Jing
M-Y
MY
Wang
J-F
JF
Weng
X-Y
XY
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D005508:Food Deprivation; D007031:Hypothalamus; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D015740:Calcitonin Gene-Related Peptide