The hypothalamic neuropeptide, QRFP, regulates high fat diet intake in female Long-Evans rats following ovariectomy

Abstract

Obesity rates in women continue to increase throughout the lifespan and obesity-related comorbidities are prevalent in women in estrogen deficiency. The hypothalamic neuropeptide, QRFP, is an orexigenic peptide that increases the intake of high fat diet (HFD) in female rats and is overexpressed following ovariectomy (OVX). Therefore, the goal of the current series of experiments was to elucidate the effect of QRFP on HFD intake following OVX and determine if QRFP-26 administration in ovariectomized females altered expression of prepro-neuropeptide Y (NPY), agouti-related peptide (AgRP) and proopiomelanocortin (POMC) mRNA in the mediobasal hypothalamus (MBH) and prepro-orexin in the lateral hypothalamus (LH). The intake of HFD was measured following acute administration of QRFP-26 prior to or following estradiol benzoate (EB) treatment in ovariectomized females. When administered prior to EB treatment, QRFP-26 increased HFD intake. EB treatment attenuated the effects of QRFP-26 on HFD intake. Sub-chronic, continuous administration of QRFP-26 increased HFD intake and weight gain following OVX. Subchronic, continuous administration of QRFP siRNA into the 3rd ventricle via osmotic pump decreased prepro-QRFP mRNA levels in the MBH by ∼75%, decreased HFD intake and decreased weight gain following OVX. QRFP-26administration did not alter the expression of prepro-NPY, AgRP or POMC mRNA in the MBH, but decreased prepro-orexin mRNA in the LH of ovariectomized females. Overall, results from these studies support the orexigenic neuropeptide, QRFP, as an important mediator of the ingestion of highly palatable foods and subsequent weight gain in females during estrogen deficiency.