Effects of exercise and phytoestrogens on white adipose tissue health in estrogen deficient rodents
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Obesity is more prevalent in menopausal women and has been linked to systemic metabolic dysfunction, insulin resistance (IR), and white adipose tissue (WAT) inflammation increasing susceptibility for cardiovascular disease, type 2 diabetes, and many types of cancer. Ovariectomy (OVX) in rodents, a model of human menopause, is associated with reduced energy expenditure (EE), IR, weight gain primarily via increased adiposity, and WAT inflammation. Exercise and dietary phytoestrogen interventions can improve metabolic and WAT health in menopausal women and OVX rodents. The studies in this dissertation were designed to investigate the visceral WAT underlying mechanisms to determine how voluntary wheel running (Chapter 3) or a diet rich in phytoestrogens (SOY) (Chapter 4) can improve WAT health following OVX in rodents. Female OVX rats selectively bred for high (HCR) or low (LCR) intrinsic aerobic capacity were fed a high fat diet (HFD; 45%) to induce obesity and had access to a running wheel. It was demonstrated that 11 weeks of voluntary wheel running improved WAT health in previously sedentary LCR rats and an adiposity gain in HCR rats presented with higher WAT inflammation despite a high volume of wheel running. Secondly, previous research in our laboratory showed SOY-mediated improvements in insulin sensitivity and visceral WAT health in OVX LCR rats. Therefore, we investigated whether the molecular mechanism behind the beneficial effects of SOY required estrogen receptor alpha (ER[alpha]). Female mice null for ER[alpha] ([alpha]KO) did not increase adiposity or alter insulin sensitivity following OVX, unlike wildtype (WT) controls and ER[beta] knockouts ([beta]KO). In addition, [alpha]KO mice were unresponsive to SOY-mediated improvements in body composition, EE, insulin sensitivity, and WAT inflammation. In OVX WT and [beta]KO mice, SOY increased spontaneous physical activity (SPA) with preservation of lean mass (all p<0.05). These data support that ER[alpha] plays a critical role in maintaining systemic metabolic health following OVX in aged mice, and suggest that ER[alpha] mediated many of the protective metabolic effects of SOY following OVX in rodents. To further investigate SOY-mediated effects on insulin signaling (i.e., phosphorylated Akt) in visceral WAT, primary adipocyte cell culture revealed insulin signaling occurred independent of ER[alpha], with no estrogen or phytoestrogen effects. Collectively, these data lend important insight into the underlying mechanisms by which daily physical activity and phytoestrogen intake during estrogen deficiency improve overall systemic and WAT health.
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