Effects of Ovariectomy on Body Weight, Metabolic Hormones and Neuroreceptors in Rats

Introduction: Obesity effects over 40% of American adults, and as of 2019, Oklahoma ranks 4th in the US in the incidence of obesity. Particularly concerning is the greater incidence of obesity in women, especially after menopause. This specific area of health issues has not been greatly studied. We model post-menopausal weight gain in ovariectomized (OVX) rats and recently reported that post-OVX weight gain is accompanied by changes in neuroimmune signaling in central nervous system (CNS) regions that respond to metabolic hormones including leptin, ghrelin and insulin. Research Question: Our working hypothesis is that alterations in neuroimmune factors involved in post-OVX weight gain are associated with changes in metabolic hormones and/or in their CNS receptors.

Study Design/Methods: In this study, 90 day old female Sprague-Dawley rats were divided into groups of OVX (n=24) or sham OVX (aka control, n=24). Rats were housed individually in plexiglass cages on a 12:12 dark:light cycle and given ad libitum access to standard laboratory chow and water throughout the experiment. After acclimation to the colony room, rats were bilaterally OVX or sham OVX and body weights were recorded daily for 5 days postoperatively. One subgroup of rats (OVX: n=8, sham: n=8), was sacrificed on day 5. Remaining subgroups of rats were weighed weekly thereafter and sacrificed at 33 (OVX: n=8, sham: n=8) or 54 (OVX: n=8, sham: n=8) days post-operatively. At termination, body weight was determined and brains and plasma were collected. Brain punches were obtained from the arcuate nucleus (ARC), dorsal vagal complex (DVC), and paraventricular nucleus (PVN) and then homogenized. ELISA kits were used to measure leptin, ghrelin and insulin receptor expression in these brain regions, in addition to circulating insulin, ghrelin and leptin levels.

Results: Body weight increased rapidly and progressively in OVX rats but not in sham OVX rats. Plasma leptin levels increased over time, especially in OVX rats, while plasma ghrelin and insulin levels were increased more transiently. Insulin, ghrelin and leptin receptor levels in the ARC did not differ between OVX and sham OVX rats after an initial increase in leptin receptor levels. In the DVC, insulin receptor levels decreased over time in OVX rats and were significantly less than those in sham OVX rats by day 54; however, neither ghrelin or leptin receptor levels differed. In the PVN, all receptor levels were reduced in OVX rats by day 54, with the leptin receptor levels also less at day 33.

Conclusions: These results do not demonstrate a clear relationship among body weight gain, circulating hormone levels, and hormone receptors in OVX rats. Nonetheless, an inverse relationship between circulating leptin and leptin receptor levels that occur with body weight gain in OVX rats was evident in the PVN. Moreover, the PVN showed the largest change in hormone receptor levels, suggesting it is an area of interest to understand hormone effects in the CNS and their role in body weight gain.

Acknowledgements: funding provided by OSU-CHS intramural award (KSC); OCAST HR18-089 (KSC)