Co‐expression of Orexin‐B and Corticotropin‐Releasing Factor in Hypothalamic Neurons of the Ovariectomized Female on a High Fat Diet

Abstract

The hypothalamic paraventricuar nucleus (PVH) is known to play a pivotal role in energy balance and in autonomic and neuroendocrine control. The neuropeptides orexin‐A (OX‐A) and orexin‐B (OX‐B) have been implicated in these homeostatic mechanisms. This study was done to investigate whether 17β‐estradiol (E) treatment coupled with ingestion of a high fat diet (HFD; 45 kcal fat) altered OX immunoreactivity in PVH of ovariectomized (OVX) female Wistar rats treated (OVX+E) or not‐treated with E (OVX only). Animals were placed on a normal diet (ND) or HFD for a period of 7 or 20 weeks. Twenty‐four hours before sacrifice all animals were given an intracerebroventricular injection of colchicine and the forebrains were processed for OX‐A‐and OX‐B‐ immunoreactivity. In all cases, relative OX‐B immunoreactive fiber density was greater throughout PVH compared to OX‐A in both female groups regardless of the diet. OX‐A‐immunoreactivity was also found to be greater in females fed a HFD compared to a ND. Furthermore, a distinct cluster of OX‐B immunoreactive neurons was found within the medial parvocellular PVH in OVX only animals, and the number of these neurons was found to higher in those fed a HFD for the longer period. Pre‐pro‐orexin protein expression was up‐regulated in PVH in OVX only females on the HFD compared to ND and compare to OVX+E on a HFD or ND. As the location of these OX‐B neurons in the medial parvocellular PVH overlapped the area known to contain corticotropin‐releasing factor (CRF) neurons, a double immunofluorescence studied was done to determine whether the OX‐B neurons co‐expressed CRF. All medial parvocellular PVH neurons that expressed OX‐B co‐expressed CRF, while not all neurons expressing CRF co‐expressed OX‐B. As OX has been shown to function as a neuromodulatory hormone that stimulates the adrenal corticotrophin hormone‐mediated response to stress, these findings suggest that in females without E, co‐release of OX‐B and CRF in response to a HFD stressor may affect anterior pituitary function.Support or Funding InformationSupported in part by the Heart and Stroke Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.