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Exercise, Epinephrine and IL-6 Mediated Regulation of Adipose Tissue Metabolism Open Access


Other title
adipose tissue
hig fat diet
Type of item
Degree grantor
University of Alberta
Author or creator
Wan, Zhongxiao
Supervisor and department
Catherine Chan (Physiology and Nutrition,Department of Agricultural, Food and Nutritional Science, University of Alberta)
David Wright (Department of human health and nutrition science, University of Guelph
Examining committee member and department
Raylene Reimer (Faculty of Kinesiology, University of Calgary)
Walter Dixon (Department of Agricultural, Food and Nutritional Science, University of Alberta)
Catherine Field (Department of Agricultural, Food and Nutritional Science, University of Alberta)
René Jacobs (Department of Agricultural, Food and Nutritional Science, University of Alberta)
Department of Agricultural, Food, and Nutritional Science
Nutrition & Metabolism
Date accepted
Graduation date
Doctor of Philosophy
Degree level
The biochemical and molecular mechanisms underlying the beneficial effects of exercise remain elusive. Growing evidence suggests that white adipose tissue (WAT) is an important organ that exercise exerts beneficial effects on. The role of interleukin 6 (IL-6) in mediating WAT metabolism remains under debate. The first objective of this thesis is to understand exercise, epinephrine and IL-6 in modulating pyruvate dehydrogenase kinase 4 (PDK4) and phosphoenolpyruvate carboxykinase (PEPCK) gene expression in WAT. Exercise and epinephrine increased PDK4 mRNA levels in WAT from lean rats. The effects of epinephrine on PDK4 were mediated via p38 mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor gamma (PPAR). The ability of exercise and epinephrine to induce PDK4 mRNA was maintained in obese rats. In contrast to epinephrine, IL-6 decreased the gene expression and protein content of PEPCK and PDK4 in cultured WAT. Although an acute bout of treadmill running did not activate IL-6 signalling in adipose tissue, the exercise-induced increases in PEPCK and PDK4 mRNA were attenuated in WAT from IL-6-/- mice. The second broad objective of this thesis was to understand the role of IL-6 in mediating WAT metabolism by utilizing IL-6-/- mice fed a high fat diet (HFD). IL-6-/- HFD mice were more glucose and insulin intolerant than wild type controls and this was mirrored by reductions in the insulin-stimulated activation of protein kinase B (PKB) and increases in the phosphorylation of extracellular signal regulated kinases (ERK) and c-Jun N-terminal kinases (JNK) in WAT. Epinephrine stimulated lipolysis and hormone sensitive lipase (HSL) phosphorylation were blunted, adiponectin mRNA expression and secretion, and AMPK phosphorylation were reduced in WAT from IL-6-/- mice. These results suggest a unique role for IL-6 in the maintenance of adipose tissue metabolism during the development of insulin resistance. In summary, exercise, similar to thiazolidinediones (TZDs), is a potent stimulus that can induce WAT glyceroneogenic enzymes. IL-6 is essential for the metabolic homeostasis in WAT under conditions of metabolic stress: exercise and chronic nutrient excess.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Zhongxiao Wan et al. (2010) Am J Physiol Cell Physiol.
Wan et al. (2012) Obesity (Silver Spring)
Wan et al. (2012) PLoS One. 2012

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