Glucocorticoid regulation of body composition and metabolism

Abstract

Glucocorticoids (GCs) are critical in maintaining energy homeostasis. Chronic excessive GC exposure, as seen in Cushing’s syndrome (CS), profoundly impacts body composition and metabolism by causing whole-body insulin resistance and abdominal adiposity. Peripheral insulin resistance occurs due to impaired insulin signaling and glucose uptake. Excess GCs lead to muscle atrophy which is associated with elevated plasma fatty acids and triglycerides, altered hepatic carbohydrate and lipid metabolism, and impaired pancreatic β-cell function. GCs also reduce bone density by increasing bone resorption while inhibiting bone formation, in part by decreasing osteoblast number and function. Lastly, a variety of skin manifestations result from GC excess. The current review explores GC regulation of body composition and metabolism. While physiological exposure to GCs and a dynamic HPA axis that is responsive to metabolic and environmental cues are essential for the survival of any organism, chronic exposure to even subtle GC excess causes the development of excess abdominal and ectopic adipose tissue, dyslipidemia, cardiovascular disease, and ultimately decreased survival.