Department of Physiology, LSU Health Sciences Center-NO, New Orleans, LA 70112, USA.
Department of Physiology, LSU Health Sciences Center-NO, New Orleans, LA 70112, USA; Joint Diabetes, Endocrinology & Metabolism Program, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Peptides. 2023 Apr;162:170960. doi: 10.1016/j.peptides.2023.170960. Epub 2023 Jan 21.
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.
女性的肥胖率在整个生命周期中持续上升，与肥胖相关的合并症在雌激素缺乏的女性中很常见。下丘脑神经肽 QRFP 是一种食欲肽，可增加雌性大鼠高脂肪饮食（HFD）的摄入量，并在卵巢切除（OVX）后过度表达。因此，本系列实验的目的是阐明 QRFP 在 OVX 后对 HFD 摄入的影响，并确定 QRFP-26 在去卵巢雌性动物中的给药是否改变了中脑基底部（MBH）前原神经肽 Y（NPY）、刺鼠相关肽（AgRP）和前阿黑皮素原（POMC）mRNA 的表达以及外侧下丘脑（LH）中的前原食欲素。在去卵巢雌性动物中，在给予雌二醇苯甲酸（EB）治疗之前或之后急性给予 QRFP-26 后，测量 HFD 的摄入量。当在 EB 治疗之前给予时，QRFP-26 增加了 HFD 的摄入量。EB 治疗减弱了 QRFP-26 对 HFD 摄入量的影响。慢性、连续给予 QRFP-26 增加了去卵巢后 HFD 的摄入量和体重增加。通过渗透泵将 QRFP siRNA 慢性、连续给予第三脑室，可使 MBH 中的前原 QRFP mRNA 水平降低约 75%，降低去卵巢后 HFD 的摄入量和体重增加。QRFP-26 给药不会改变 MBH 中前原 NPY、AgRP 或 POMC mRNA 的表达，但会降低去卵巢雌性动物 LH 中的前原食欲素 mRNA。总的来说，这些研究的结果支持食欲肽 QRFP 作为雌激素缺乏时女性摄入高美味食物和随后体重增加的重要介质。
