Chronic glucocorticoid exposure causes brown adipose tissue whitening, alters whole-body glucose metabolism and increases tissue uncoupling protein-1.

ABSTRACT

Adipose tissue (AT) has been found to exist in two predominant forms, white and brown. White adipose tissue (WAT) is the body's conventional storage organ, and brown adipose tissue (BAT) is responsible for non-shivering thermogenesis which allows mammals to produce heat and regulate body temperature. Studies examining BAT and its role in whole-body metabolism have found that active BAT utilizes glucose and circulating fatty acids and is associated with improved metabolic outcomes. While the beiging of WAT is a growing area of interest, the possibility of the BAT depot to "whiten" and store more triglycerides also has metabolic and health implications. Currently, there are limited studies that examine the effects of chronic stress and its ability to induce a white-like phenotype in the BAT depot. This research examined how chronic exposure to the murine stress hormone, corticosterone, for 4 weeks can affect the whitening process of BAT in C57BL/6 male mice. Separate treatments with mirabegron, a known ß3-adrenergic receptor agonist, were used to directly compare the effects of corticosterone with a beiging phenotype. Corticosterone-treated mice had significantly higher body weight (p ≤ 0.05) and BAT mass (p ≤ 0.05), increased adipocyte area (p ≤ 0.05), were insulin resistant (p ≤ 0.05), and significantly elevated expressions of uncoupling protein 1 (UCP-1) in BAT (p ≤ 0.05) while mitochondrial content remained unchanged. This whitened phenotype has not been previously associated with increased uncoupling proteins under chronic stress and may represent a compensatory mechanism being initiated under these conditions. These findings have implications for the study of BAT in response to chronic glucocorticoid exposure potentially leading to BAT dysfunction and negative impacts on whole-body glucose metabolism.