New findings: What is the central question of this study? Does glucocorticoid excess disrupt brown adipose tissue (BAT) phenotype and function? What is the main finding and its importance? Glucocorticoid excess induced an extensive remodelling of interscapular BAT, resulting in a white-like phenotype in association with metabolic disturbances. Glucocorticoids might be an important modulator of BAT physiology and BAT may have a role in pathophysiology of metabolic disturbances induced by glucocorticoid excess.
Abstract: In mammals, brown adipose tissue (BAT) is centrally involved in energy metabolism. To test the hypothesis that glucocorticoid excess disrupts BAT phenotype and function, male Wistar rats were treated with corticosterone in drinking water for 21 days. To confirm induction of glucocorticoid excess and metabolic disturbances, adrenal weight, corticotrophin releasing hormone mRNA levels and corticosterone serum levels were measured and a glucose tolerance test and serum triacylglycerol analyses were performed. Adipose tissue deposits were excised, weighed and evaluated by a set of biochemical, histological and molecular procedures, including thin-layer chromatography, histochemistry, immunohistochemistry, quantitative real-time polymerase chain reaction, high-resolution oxygraphy, ATP synthesis and enzymatic activity measurements. The approach was successful in induction of glucocorticoid excess and metabolic disturbances. Lower body weight and increased adiposity were observed in corticosterone-treated rats. Interscapular brown adipose tissue (iBAT) showed higher sensitivity to glucocorticoids than other fat deposits. The treatment induced lipid accumulation, unilocular rearrangement, increased collagen content and decreased innervation in iBAT. Furthermore, expression of Prdm16 (P < 0.05), Ucp1 (P <0.05) and Slc7a10 (P <0.05) mRNA decreased, while expression of Fasn (P <0.05) and Lep (P <0.05) mRNA increased in brown adipose tissue. Also, the levels of UCP1 diminished (P <0.001, 2.5-fold). Finally, lower oxygen consumption (P <0.05), ATP synthesis (P <0.05) and mitochondrial content (P <0.05) were observed in iBAT of glucocorticoid-treated rats. Glucocorticoid excess induced an extensive remodelling of interscapular brown adipose tissue, resulting in a white-like phenotype in association with metabolic disturbances.
Keywords: brown adipose tissue; glucocorticoids; metabolic disturbances.
© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.