Osteopontin Expression is Upregulated in Gonadal Adipose Tissue During Early Menopause Stage in Female Mice

Abstract

Background: Menopausal women are at high risk of developing atherosclerosis. Reduced ovarian hormone production is a key feature of menopause, and it often leads to increased visceral adiposity and atherosclerosis. Osteopontin (OPN) is an inflammatory cytokine found in high levels in menopausal women, and in human atherosclerotic plaque. While recent studies report that macrophages in male epididymal white adipose tissue are able to produce OPN, less is known about the gonadal white adipose tissue (gWAT) in females. We hypothesize that OPN protein expression is up-regulated in gWAT in early stages of menopause, conferring gWAT as a source of OPN.Methods: To address our hypothesis, a bilateral ovariectomy in a surgical menopausal murine model was utilized. Twelve-week-old female C57BL/6 sexually mature mice were randomized into two experimental groups: Sham group (n=5) whose ovaries remained intact, and OVX group (n=6), who underwent ovariectomies, and were observed for four weeks therafter. At terminal experiments, gonadal white adipose tissue (gWAT) was collected for biochemical analysis. Results: As expected, OVX mice exhibited increased body weights (24.07 ± 0.85 g vs 21.06 ± 0.38 g controls, p<0.05) and increased gWAT mass (13.69 ± 1.421 mg/g vs 9.58 ± 0.55 mg/g control, p<0.05), indicating that early decline in female hormones is able to promote adiposity. Strikingly, greater OPN expression (2.57 ± 0.50 a.u vs. 0.76 ± 0.13 a.u sham group, n=3, p<0.05) was observed in the gWAT from the OVX group. Conclusion: Our results indicate that OPN expression in gWAT is increased during early stages of menopausal status, and suggest that gWAT could be a potential source of high levels of OPN in menopause. Our data suggest that female gWAT is not only an expanded fat depot but a metabolically active tissue contributing to an inflammatory state in menopause by an increased production of circulating cytokines such as OPN, which can ultimately contribute to inflammatory processes, including atherosclerosis. Funding: Diabetes Action to Maria Alicia Carrillo Sepulveda This is the full abstract presented at the American Physiology Summit 2023 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.