Date of Award

Spring 1-1-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Integrative Physiology

First Advisor

Monika Fleshner

Second Advisor

Christopher Lowry

Third Advisor

Paul MacLean

Fourth Advisor

Robert Mazzeo

Fifth Advisor

Douglas Seals

Abstract

Exposure to intense acute stress evokes an increase in the expression of systemic and local inflammatory proteins. In the short term, this sterile inflammatory response is adaptive and required for host-defense but when repeated or sustained, can promote disease. White adipose tissue (WAT) has emerged as a metabolic organ capable of expressing numerous inflammatory-associated proteins, however little is known about these proteins in the absence of obesity. Habitual exercise and fasting have also been reported to modulate the effects of stress on immune function, however, the impact of stress on cytokine expression in the WAT of lean, physically active or fasted rats remains unclear. The purpose of this dissertation was to identify the impact of acute stress, habitual exercise and fasting on systemic and WAT-related inflammatory protein expression in lean rats. In chapters 1 and 2 we examined the effects of habitual exercise or a 24-h fast on stress-evoked cytokines in the blood and subcutaneous, intraperitoneal and visceral WAT. We then presented evidence in chapter 3 supporting the hypothesis that, when repeatedly induced, stress-evoked interleukin-1 beta contributes toward the development of visceral obesity. This dissertation demonstrates four novel findings: 1) sustained activation of the stress response stimulates the production of inflammatory-related proteins in lean WAT; 2) stress-evoked cytokine expression in WAT is unique based upon the protein and the anatomical location of the depot; 3) by potentiating stress-evoked cytokines and increasing IL-10, habitual exercise may optimize the control of stress-evoked cytokine expression in WAT and; 4) a 24-h fast reduces the expression of pro-inflammatory cytokines in visceral WAT without disrupting the inflammatory arm of the stress response. These findings demonstrate that activation of the stress response plays a modulatory role in the expression of WAT-related inflammatory proteins and collectively suggest that habitual exercise and fasting tip the cytokine balance in WAT toward a more anti-inflammatory profile. Given that repeated exposure to stressors can promote the development of visceral obesity, chronic inflammation and insulin resistance, these data suggest a novel mechanism whereby habitual exercise and fasting may promote metabolic health and/or protect against the negative consequences of stress.

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