ORIGINAL ARTICLE: The approach to the mechanism of calcitonin gene-related peptide-inducing inhibition of food intake

Abstract

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.

Mapping of CGRP in the alpaca diencephalon

“…It has been suggested that CGRP reduces food intake by means of suppressing orexigenic neuropeptides and/or stimulating anorexigenic neuropeptides expression in the hypothalamus (Sun et al, 2010). CGRP downregulated neuropeptide Y mRNA levels, but up regulated colecistokinin mRNA expression (Sun et al, 2010). These data suggest that the CGRP could be involved in the food intake response in the alpaca.…”

“…It has been demonstrated that the anorectic effect exerted by the CGRP is specific, since the peptide decreases food intake without causing overt signs of discomfort or malaise and without inducing a conditioned taste aversion (Morley et al, 1996). It has been suggested that CGRP reduces food intake by means of suppressing orexigenic neuropeptides and/or stimulating anorexigenic neuropeptides expression in the hypothalamus (Sun et al, 2010). CGRP downregulated neuropeptide Y mRNA levels, but up regulated colecistokinin mRNA expression (Sun et al, 2010).…”

Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system

“…The direct activation of GPCRs expressed in sensory afferent neuronal fibers within lymphatic vessels by lymphatic fluid allows the intestinal contents and interstitial paracrine agents to act like hormones. Additionally, given the anorectic effects of central and circulating sensory neuropeptides such as CGRP (64), our data point to a new pathway for the modulation of behavior, such as food intake, by premetabolized dietary nutrients via MLF-GPCR activation of sensory nerves, which represents a neurolymphocrine system (Fig. 8).…”

Effect of daily gavage with a collagen hydrolysate containing calcitonin gene-related peptide (CGRP)-like molecules on plasma CGRP-levels in rats

“…It has been demonstrated that intraperitoneal injection of CGRP increases plasma CGRP-levels and causes a loss of appetite in rats (Sun et al, 2010). Despite gavage with SH also increasing plasma CGRP-levels, this increment (of around 70%) was much lower than that obtained by intra peritoneal injection (of around 530%), and did not exert an anorectic effect, even after 24 h of food deprivation.…”

“…CGRP is known as one of the most potent arterial and venous vasodilators (Gupta et al, 2006), with potency 10-fold greater than the prostaglandins and up to 1000 times greater than the other classic vasodilators (Brain & Grant, 2004). The capacity of CGRP to regulate the development of T cells (Bulloch, McEwen, Nordberg, Diwa, & Baird, 1998), to induce satiety (Sun, Jing, Wang, & Weng, 2010), and its ability to exert gastric acid protection (Lenz, Mortrud, Vale, Rivier, & Brown, 1984) have also been documented. Recently, the important role of a-CGRP in the local regulation of bone metabolism has been reported 1756-4646/$ -see front matter Ó 2012 Elsevier Ltd. All rights reserved.…”