Grant: Operating Grant

Owing to its vital role in locomotion and the fact that it accounts for the majority of whole body glucose disposal and fatty acid oxidation the majority of exercise physiology/biochemistry studies investigating the acute effects of exercise on glucose and fat metabolism have examined skeletal muscle. However, there is a growing appreciation for the role of adipose tissue (i.e. fat) in regulating whole body metabolism. Despite this, few if any studies have examined the acute effects of exercise in controlling the function of adipose tissue. In preliminary experiments we have found that a single bout of exercise leads to the development of impaired insulin action in adipose tissue during the recovery from exercise. This is an important adaptation as it allows for a continued release of fatty acids from adipose tissue to be used as a fuel source while sparing blood sugar to be used for the re-synthesis of glycogen in muscle and liver. The purpose of this proposal is to determine the mechanisms mediating the effects of exercise on adipose tissue insulin action. Based on strong preliminary data, we believe that a protein called interleukin 6 (IL-6) is involved in this process. We will explore the involvement of IL-6 in the regulation of adipose tissue function through using special, genetically engineered mice that do not have IL-6. We will determine how rapidly the development of adipose tissue insulin resistance reverses and will also examine how exercise modifies adipose tissue insulin action in obese, insulin resistant mice. These studies will provide novel insight into the mechanisms through which exercise controls the function of adipose tissue during the recovery from exercise. More importantly our studies will provide new information regarding the mechanisms of how adipose tissue becomes dysfunctional during the development of obesity and insulin resistance and how exercise can be used to treat this condition.