Examining the mechanisms for the lipolytic and antilipolytic effects of glucocorticoids in adipose tissue

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Glucocorticoids (GCs) are naturally produced steroid hormones released by the activation of the hypothalamo-pituitary-adrenal (HPA) axis in a circadian rhythm and during times of stress (such as with exercise or starvation). GCs such as cortisol (humans) or corticosterone (rodents) have long been thought to be critical in helping to mobilize energy substrates for the organism when energy demands may be high and perhaps when food is relatively scarce (i.e. during fasting or during prolonged exercise). It is without controversy that GCs increase blood glucose levels by increasing hepatic glucose production and by limiting glucose disposal into skeletal muscle. Most texts, journals and websites also state that GCs help mobilize free fatty acids (FFAs) from adipocytes to help provide fuel for energy metabolism during exercise and a stress response by increasing adipose tissue lipase expression and/or activity. However, we and others have recently begun to discover that GCs, in fact, rapidly lower lipolysis rates in a dose-dependent fashion in fat cells and reduce FFA mobilization, at least in the short term. The purpose of this program renewal is to determine the physiological relevance of increases in GCs during times of stress (i.e. exercise, fasting, neurogenic stress) and the underlying mechanisms by which GCs have opposing roles in adipose tissue mobilization. We hypothesize that while GCs may change the "machinery" for lipolysis by changing gene transcription of key rate limiting lipases, they are actually antilipolytic via rapid non-genomic actions. The experiments that are outlined in this proposal will provide novel and important information about how GCs alter adipose tissue metabolism during a stress response. This research continues to provide an outstanding environment for trainees in the field of physiology and metabolism who are interested in Natural Sciences.