Exercise Decreases Estrogen Receptor β and Inflammatory Cytokines in the Mesenteric Fat of an Endometriosis Rat Model

Abstract

Endometriosis, a gynecological disorder, is characterized by increased levels of the estrogen receptor β (ERβ) in endometrial tissue. Estrogen receptors (ER) are also present in visceral fat and dysregulation of their function is known to correlate with increased white adipose tissue. Preliminary data in our lab found increased mesenteric fat and serum leptin levels in endometriosis animals, which are decreased by exercise. In rodents, morphology of the mesenteric fat can be regulated by exercise, however it is still unclear what role exercise plays in this change and how it might impact inflammatory conditions such as endometriosis.HypothesisVoluntary exercise can decrease endometriosis through modulation of ER in the mesenteric fat and a decrease in inflammatory cytokines.MethodsEndometriosis (ENDO) was induced in female Sprague Dawley rats by the implantation of uterine tissue next to the intestinal mesentery while control group (SHAM) received only sutures. The exercised endometriosis group (ENDO‐Ex) had access to a running wheel before and after surgery. After sixty days, rats were sacrificed and mesenteric fat was collected for measurement of ERβ, ERα, interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) by RT‐PCR. After fixation and staining with hematoxylin & eosin micro‐sections of mesenteric fat were analyzed to ascertain adipocyte morphology and their number and size.ResultsThe Endo animals had significantly higher amounts of mesenteric fat in contrast with the SHAM (p<0.05) and the ENDO‐Ex animals (p<0.01; n=9–10/group). The serum leptin hormone levels were significantly decreased in ENDO‐Ex animals when compared with the SHAM (p<0.001) and ENDO (p<0.001) animals. Across all groups a significant correlation was found between percentage of fat/body weight and ER‐β (p=0.011; n=12). Increased mesenteric fat also correlated with increased levels of IL‐1β (p=0.024) and IL‐6 (p=0.030) in the endometriosis animals (n=4/group). ENDO‐Ex animals developed less endometriotic lesions and these were smaller in size. Exercise significantly decreased ERβ levels (p=0.045) and IL‐1β (p=0.008, n=4/group) compared with ENDO. No significant differences were found in ERα levels between groups.ConclusionOur results demonstrate that exercise can reverse the increased levels of mesenteric fat, ERβ and inflammatory cytokines found in an animal model of endometriosis.Support or Funding InformationP20GM103475‐16, R15AT009915 & R25GM096955