Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide expressed both centrally and peripherally. CGRP has been shown to be involved in arteriolar dilation, cardiovascular regulation, pain transmission, migraine, and gastrointestinal physiology. Our current research is aimed at analyzing CGRP's impact on appetite/satiety, body metabolism, and energy homeostasis. Our study investigated the effects of a single-dose intraperitoneal (IP) treatment with CGRP on food and water consumption, energy expenditure, physical activity, respirometry, and a panel of plasma metabolic hormones in C57Bl/6 wild-type (WT) mice. After a CGRP IP injection at a dose of 2 nmol (10 μM CGRP in 200 μl of saline), a significant reduction in food intake and metabolic parameters as RQ, VCO₂, and VO₂ was observed. CGRP-injected mice had also significantly lower total energy expenditure (TEE) with no changes in activity levels compared to vehicle-injected controls. CGRP treatment in mice induced significantly lower plasma levels of glucagon and leptin but higher levels of amylin. Our data show that a single dose of CGRP peptide significantly decreased food consumption and altered calorimetric parameters and plasma metabolic hormone levels, thus confirming that CGRP plays a pivotal role in the regulation of appetite and metabolism. Future studies are necessary to analyze CGRP's long-term impact on body metabolism and its potential effects on appetite, obesity, and metabolic disorders.

Background: High-protein diets (HPDs) recently have been used to obtain body weight and fat mass loss and expand muscle mass. Several studies have documented that HPDs reduce appetite and food intake.Objective: Our goal was to determine the long-term effects of an HPD on body weight, energy intake and expenditure, and metabolic hormones.Methods: Male C57BL/6 mice (8 wk old) were fed either an HPD (60% of energy as protein) or a control diet (CD; 20% of energy as protein) for 12 wk. Body composition and food intakes were determined, and plasma hormone concentrations were measured in mice after being fed and after overnight feed deprivation at several time points.Results: HPD mice had significantly lower body weight (in means ± SEMs; 25.73 ± 1.49 compared with 32.5 ± 1.31 g; P = 0.003) and fat mass (9.55% ± 1.24% compared with 15.78% ± 2.07%; P = 0.05) during the first 6 wk compared with CD mice, and higher lean mass throughout the study starting at week 2 (85.45% ± 2.25% compared with 75.29% ± 1.90%; P = 0.0001). Energy intake, total energy expenditure, and respiratory quotient were significantly lower in HPD compared with CD mice as shown by cumulative energy intake and eating rate. Water vapor was significantly higher in HPD mice during both dark and light phases. In HPD mice, concentrations of leptin [feed-deprived: 41.31 ± 11.60 compared with 3041 ± 683 pg/mL (P = 0.0004); postprandial: 112.5 ± 102.0 compared with 8273 ± 1415 pg/mL (P < 0.0001)] and glucagon-like peptide 1 (GLP-1) [feed-deprived: 5.664 ± 1.44 compared with 21.31 ± 1.26 pg/mL (P = <0.0001); postprandial: 6.54 ± 2.13 compared with 50.62 ± 11.93 pg/mL (P = 0.0037)] were significantly lower, whereas postprandial glucagon concentrations were higher than in CD-fed mice.Conclusions: In male mice, the 12-wk HPD resulted in short-term body weight and fat mass loss, but throughout the study preserved body lean mass and significantly reduced energy intake and expenditure as well as leptin and GLP-1 concentrations while elevating postprandial glucagon concentrations. This study suggests that long-term use of HPDs may be an effective strategy to decrease energy intake and expenditure and to maintain body lean mass.