Impact of exercise on uncoupling protein 1 and macrophage phenotype in mesenteric adipose tissue in an animal model of endometriosis

Abstract

Endometriosis is a gynecological disorder characterized by growth of endometrial tissue outside the uterine cavity, with symptoms which may include chronic pelvic pain and infertility resulting in a decreased quality of life. Previous studies in our laboratory demonstrated that endometriosis animals have increased mesenteric adipose tissue (MAT), inflammation, and growth of implanted endometrial vesicles which are decreased by voluntary exercise. The levels of Uncoupling Protein 1 (UCP-1), a mitochondrial protein, are known to be increased by exercise in rodents, promoting thermogenesis and decreasing inflammation. Exercise can also increase expression of peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily. When activated PPARγ polarizes the macrophages into an anti-inflammatory M2 state, which can stimulate white adipose tissue beiging. We hypothesized that voluntary wheel running exercise can increase UCP-1 and M2 macrophages, decreasing MAT and endometrial vesicle size. Aim: To assess the impact of voluntary exercise on UCP-1 expression and macrophage phenotype in MAT of an animal model of endometriosis. Methods: Endometriosis was induced by implanting uterine tissue on the intestinal mesentery of female Sprague Dawley rats while control group only received sutures (SHAM). Exercise rats had access to a running wheel after surgery (ENDO-EX or SHAM-EX), while non-exercised animals didn’t (ENDO and SHAM; n=10-11/group). After sixty days, animals were sacrificed, and MAT was collected to determine CD68, UCP-1 and PPARγ expression by immunofluorescence staining. Results: Vesicles from ENDO-EX animals exhibited significantly decreased average weight (p<0.01) and smaller average total area (p<0.01) compared with the ENDO group. Endometriosis animals showed increased mesenteric adipose tissue when compared to sham group (p<0.01), which was reduced by voluntary exercise (p<0.001). Macrophage infiltration, UCP-1 and PPARγ expression increased with exercise. Conclusions: Increased UCP-1 and anti-inflammatory M2 macrophages following exercise may result in browning of MAT which can have a role in reducing the development of vesicles in the endometriosis model. These findings suggest that exercise may be a potential complementary therapeutic strategy for managing endometriosis symptoms. This work was supported by R15AT009915, R16GM149365, T32GM144896, PRI MD Summer Program and Porter Physiology Development Fellowship. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.