The Metabolic Implications of Glucocorticoids in a High-Fat Diet Setting and the Counter-Effects of Exercise

Glucocorticoids (GCs) are steroid hormones, naturally produced by activation of the hypothalamic-pituitary-adrenal (HPA) axis, that mediate the immune and metabolic systems. Synthetic GCs are used to treat a number of inflammatory conditions and diseases including lupus and rheumatoid arthritis. Generally, chronic or high dose GC administration is associated with side effects such as steroid-induced skeletal muscle loss, visceral adiposity, and diabetes development. Patients who are taking exogenous GCs could also be more susceptible to poor food choices, but the effect that increasing fat consumption in combination with elevated exogenous GCs has only recently been investigated. Overall, these studies show that the damaging metabolic effects initiated through exogenous GC treatment are significantly amplified when combined with a high fat diet (HFD). Rodent studies of a HFD and elevated GCs demonstrate more glucose intolerance, hyperinsulinemia, visceral adiposity, and skeletal muscle lipid deposition when compared to rodents subjected to either treatment on its own. Exercise has recently been shown to be a viable therapeutic option for GC-treated, high-fat fed rodents, with the potential mechanisms still being examined. Clinically, these mechanistic studies underscore the importance of a low fat diet and increased physical activity levels when individuals are given a course of GC treatment.