Hypothalamic QRFP: regulation of food intake and fat selection

Abstract

QRFP, a member of the RFamide-related peptide family, is a strongly conserved hypothalamic neuropeptide that has been characterized in various species. Prepro-QRFP mRNA expression is localized to select regions of the hypothalamus, which are involved in the regulation of feeding behavior. The localization of the peptide precursor has led to the assessment of QRFP on feeding behaviors and the orexigenic effects of QRFP have been detected in mice, rats, and birds. QRFP acts in a macronutrient specific manner in satiated rats to increase the intake of a high fat diet, but not the intake of a low fat diet, and increases the intake of chow in food-restricted rats. Studies suggest that QRFP's effects on food intake are mediated by the adiposity signal, leptin, and hypothalamic neuropeptides. Additionally, QRFP regulates the expression and release of hypothalamic Neuropeptide Y and proopiomelanocortin/α-Melanocyte-Stimulating Hormone. QRFP binds to receptors throughout the brain, including regions associated with food intake and reward. Taken together, these data suggest that QRFP is a mediator of motivated behaviors, particularly the drive to ingest high fat food. The present review discusses the role of QRFP in the regulation of feeding behavior, with emphasis on the intake of dietary fat.

Fig. 1

The effects of intracerebroventricular administration of QRFP-26 on low fat (10 % kcal from fat) and high fat food intake (60 % kcal from fat). a QRFP-26 selectively increased high fat food intake at 1 h, 2 h, 4 h, and 6 h following administration in male rats. b QRFP-26 administration increased high fat food intake, but not low fat food intake at each time in random cycling female rats. *p < 0.05, compared to vehicle treated, data is expressed as mean ± SEM.

Fig. 2

a Intracerebroventricular administration of QRFP-43 (22.5 µg/5 µl) and the neuropeptide Y Y1 receptor antagonist, BIBP3226 (13.3 nM/5 µl), on high fat food intake (55 % kcal from fat). QRFP-43 increased high fat food intake. Administration of BIBP3226, 30 min prior to administration of QRFP-43, partially attenuated the effects of QRFP-43 (n = 6–8/group). b Intracerebroventricular administration of the MC3/MC4 agonist, MTII (1 nM/5 µl), and QRFP-43 (22.5 µg/5 µl) on high fat food intake (55 % kcal from fat). QRFP-43 increased high fat food intake. Administration of MTII, 30 min prior to administration of QRFP-43, partially attenuated the effects of QRFP-43 (n = 5–7/group). Data were analyzed by a 2 × 2 ANOVA and Bonferroni post-hoc analyses. *p < 0.05 compared to vehicle treated, data is expressed as mean ± SEM.