Exploratory analysis of estrogen-mediated gene expression in central ghrelin signaling pathways

Abstract

Introduction & Objective: As of 2020, 67% of Americans are overweight or obese. Particularly concerning is the greater incidence of obesity in post-menopausal women. Previous studies have shown that estrogen decreases food intake and body weight; however, it is not yet clear the method by which estrogen affects central pathways that regulate feeding. To address this, we used a microarray to compare estrogen-mediated changes in gene expression within the leptin signaling pathway. This pathway contains brain areas known to be involved in food intake including: the arcuate nucleus of the hypothalamus (ARC), the paraventricular nucleus of the hypothalamus (PVN), and nucleus of the solitary tract (NTS).

Methods: Adult female rats were bilaterally ovariectomized and treated with either oil or estrogen injections. After termination, RNA was collected from the ARC, PVN, and NTS. Isolated RNA was sent to Thermo Fisher Scientific for microarray analysis. Results were analyzed using Transcriptome Analysis Console software.

Results: In the brain areas investigated, we found that estrogen influenced gene expression for multiple neurotransmitters, neuroreceptors, and signaling molecules involved in the leptin signaling pathway.

Conclusion: The changes in body and uterine weights confirmed the effects of estrogen. The ARC, PVN, and NTS displayed a variety of genes regulated by estrogen, confirming that estrogen mediates gene expression within the leptin signaling pathway. This demonstrates a potential mechanism by which estrogen affects central pathways to decrease food intake and body weight.