RFamide Peptide QRFP43 Causes Obesity with Hyperphagia and Reduced Thermogenesis in Mice

Abstract

QRFP, an RFamide peptide, was recently identified as an endogenous ligand of an orphan G protein-coupled receptor, GPR103. Recent investigation revealed that acute intracerebroventricular (ICV) administration of QRFP26/P518/26RFa, a constitutive part of QRFP43 (43-amino acid-residue form of QRFP), increases appetite in mice, but its role in long-term energy homeostasis remains unknown. In the present study, we examined the effects of chronic administration of QRFP43 on feeding behavior, body weight regulation, and energy expenditure in mice. Intracerebroventricular infusion of QRFP43 for 13 d resulted in a significant increase in body weight and fat mass with hyperphagia. Weight gain and hyperphagia were more evident when mice were fed a moderately high-fat diet. Pair feeding of QRFP43-infused mice did not increase body weight but significantly increased fat mass and plasma concentrations of insulin, leptin, and cholesterol when compared with controls. Moreover, significant decreases in rectal temperature and expression of brown adipose tissue uncoupling protein-1 mRNA were observed in QRFP43-infused ad libitum- and pair-fed mice. The present results suggest that QRFP plays an important role in energy homeostasis by regulating appetite and energy expenditure.

Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis

“…The two groups show higher concentrations of circulating 26RFa compared with healthy subjects. This finding is consistent with previous data obtained in obese animal models showing an upregulation of the 26RFa system in genetically obese mice and rats fed a high-fat diet (5,8,10) and suggests that, in humans as in rodents, upregulation of the 26RFa system may play a role in the development and maintenance of the obese status. However, high plasma 26RFa levels were also detected in patients with DT1 who were not obese.…”

“…Indeed, intracerebroventricular administration of 26RFa or 43RFa stimulates food intake (1,5,8,9), and the neuropeptide exerts its orexigenic activity by modulating the neuropeptide Y/proopiomelanocortin system in the arcuate nucleus (9). Chronic injection of 43RFa induces a significant increase in mice body weight and fat mass, which is associated with a hyperphagic behavior (8), and the orexigenic activities of 26RFa and 43RFa are more robust in rodents fed a high-fat diet (8,10). Consistent with these observations, expression of prepro26RFa mRNA is upregulated in the hypothalamus of genetically obese ob/ob and db/db mice and rodents subjected to a high-fat diet (5,10).…”

“…Neuroanatomical observations revealed that 26RFa-and GPR103-expressing neurons are primarily localized in hypothalamic nuclei involved in the control of feeding behavior (1,2,5,7). Indeed, intracerebroventricular administration of 26RFa or 43RFa stimulates food intake (1,5,8,9), and the neuropeptide exerts its orexigenic activity by modulating the neuropeptide Y/proopiomelanocortin system in the arcuate nucleus (9). Chronic injection of 43RFa induces a significant increase in mice body weight and fat mass, which is associated with a hyperphagic behavior (8), and the orexigenic activities of 26RFa and 43RFa are more robust in rodents fed a high-fat diet (8,10).…”

A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice

“…Very recently, Moriya et al (34) reported that chronic administration of QRFP can cause obesity in mice. QRFPinduced weight gain under normal chow diet was marginal in their data, which were basically consistent with ours.…”

Hypothalamo-gastrointestinal axis – role in food intake regulation

“…The 43RFa also stimulates food intake and its effect is even more pronounced than the effect of 26RFa (Moriya et al, 2006;Takayasu et al, 2006). In mice, chronic injection of 43RFa evoked a hyperphagic behaviour resulting in an increase of the body weight and fat mass but also in a decrease of the energy expenditure (Moriya et al, 2006). Fasting potentiates the orexigenic activity of 26RFa.…”