Central administration of the RFamide peptides, QRFP-26 and QRFP-43, increases high fat food intake in rats

Abstract

Pyrogultamylated arginine-phenylalanineamide peptide (QRFP) is strongly conserved across species and is a member of the family of RFamide-related peptides, with the motif Arg-Phe-NH 2 at the Cterminal end. The precursor peptide for QRFP generates a 26-amino acid peptide (QRFP-26) and a 43-amino acid peptide (QRFP-43), both of which bind to the G protein-coupled receptor, GPR103. Recently, QRFP has been characterized in rats, mice and humans and has been reported to have orexigenic properties. In rodents, prepro-QRFP mRNA is expressed in localized regions of the mediobasal hypothalamus, a region implicated in feeding behavior. Increased intake of a high fat diet contributes to increased weight gain and obesity. Therefore, the current experiments investigated the effects of QRFP administration in rats and the effects of a high fat diet on prepro-QRFP mRNA and GPR103 receptor mRNA levels. Intracerebroventricular administration of QRFP-26 (3.0nM, 5.0nM) and QRFP-43 (1.0nM, 3.0nM) dose-dependently increased 1h, 2h, and 4h cumulative intake of high fat (55% fat), but not low fat (10% fat) diet. In Experiment 2, hypothalamic prepro-QRFP mRNA levels and GPR103 receptor mRNA levels were measured in rats fed a high fat or a low fat diet for 21 days. Prepro-QRFP mRNA was significantly increased in the ventromedial nucleus/ arcuate nucleus of the hypothalamus of rats fed a high fat diet compared to those fed a low fat diet, while GPR103 mRNA levels were unchanged. These findings suggest that QRFP is a regulator of dietary fat intake and is influenced by the intake of a high fat diet.

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).…”

“…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). Altogether, these observations support the notion that 26RFa could play a role in the development and maintenance of the obese status.…”

MOLECULAR EVOLUTION OF GPCRS: 26Rfa/GPR103

“…Indeed, i.c.v. injection of 26RFa/QRFP has been demonstrated to stimulate food intake in rodents (Chartrel et al 2003, Do Régo et al 2006, Moriya et al 2006, Takayasu et al 2006, Primeaux et al 2008, Lectez et al 2009, Primeaux 2011. In addition to its orexigenic effects, 26RFa/QRFP has been reported to exert a wide range of biological actions (Fig.…”

Regulation of the expression of corticotropin-releasing factor gene by pyroglutamylated RFamide peptide in rat hypothalamic 4B cells

“…QRFP has orexigenic effects in rodents [1][2][3][4][5]. QRFP also regulates behavioral arousal, blood pressure, locomotor activity, and aldosterone and insulin secretion [2,6,7].…”