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

  • Author / Creator
    Wan, Zhongxiao
  • 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.

  • Subjects / Keywords
  • Graduation date
    Fall 2012
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.