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

Specific neuronal phenotypes within the rostral ventrolateral medulla following cardiovascular deconditioning in rats

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Thesis (M.S.) University of Missouri-Columbia 2008.[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Humans exposed to prolonged periods of bed rest or spaceflight undergo multiple cardiovascular adaptations including a predisposition for orthostatic intolerance. Studies in both humans and rats suggest there may be alterations within the brain following periods of spaceflight or bed rest. The hindlimb unloaded (HU) rat model shows similar cardiovascular consequences to that of humans and exhibits an attenuated sympathoexcitatory response during a hypotensive stimulus in addition to an enhanced GABAergic ([gamma]-amino butyric-acid) inhibition at the level of the rostral ventrolateral medulla (RVLM). Nitric oxide (NO), a central neuromodulator, has been shown to increase GABA release in the central nervous system. Thus, NO may contribute to the enhanced GABAergic inhibition in the RVLM after HU. The RVLM also contains a population of catecholaminergic cells important for sympathetic nervous system regulation. We hypothesized that 14 days of HU increases the number of neuronal nitric oxide synthase and glutamic acid decarboxylase, 67 kDa isoform, (GAD67) immunoreactive cells and decreases the number of phenylethanolamine N-methyl transferase (PNMT; marker for catecholaminergic cells) cells within the RVLM. The number and distribution of nNOS, GAD67, and PNMT cells were examined using immunohistochemistry in brainstem sections (30 [micrometers]) from control and HU male rats. Contrary to our hypothesis, our results suggest that changes in the number of nNOS or PNMT or GABAergic neurons within the RVLM may not contribute to the increased GABAergic inhibition in the RVLM or the attenuation of reflex activation of sympathetic nervous system activity following 14 days of HU.Includes bibliographical references

Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity

Regular physical activity is effective in reducing visceral white adipose tissue (AT) inflammation and oxidative stress, and these changes are commonly associated with reduced adiposity. However, the impact of multiple periods of physical activity, intercalated by periods of inactivity, i.e., intermittent physical activity, on markers of AT inflammation and oxidative stress is unknown. In the present study, 5-wk-old male C57BL/6 mice were randomized into three groups (n = 10/group): sedentary, regular physical activity, and intermittent physical activity, for 24 wk. All animals were singly housed and fed a diet containing 45% kcal from fat. Regularly active mice had access to voluntary running wheels throughout the study period, whereas intermittently active mice had access to running wheels for 3-wk intervals (i.e., 3 wk on/3 wk off) throughout the study. At death, regular and intermittent physical activity was associated with similar reductions in visceral AT mass (approximately −24%, P < 0.05) relative to sedentary. However, regularly, but not intermittently, active mice exhibited decreased expression of visceral AT genes related to inflammation (e.g., monocyte chemoattractant protein 1), immune cell infiltration (e.g., CD68, CD11c, F4/80, CD11b/CD18), oxidative stress (e.g., p47 phagocyte oxidase), and endoplasmic reticulum stress (e.g., CCAAT enhancer-binding protein homologous protein; all P < 0.05). Furthermore, regular, but not intermittent, physical activity was associated with a trend toward improvement in glucose tolerance (P = 0.059). Collectively, these findings suggest that intermittent physical activity over a prolonged period of time may lead to a reduction in adiposity but with retention of a sedentary obese white AT and metabolic phenotype