Brown adipose tissue remodelling induced by corticosterone in male Wistar rats

Abstract

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.

Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk

“…Studies from our laboratory showed that corticosterone treatment resulted in lipid accumulation and a decrease in basal and norepinephrine-induced UCP1 mRNA and protein content in BAT of both male and female mice (36,146,147). These effects were confirmed by others in a study in which male rats were treated with corticosterone for 21 days (148). In in vitro differentiated brown adipocytes, GCs reduced the norepinephrine-stimulated Ucp1 mRNA expression (147,149).…”

Flattening of diurnal glucocorticoid oscillations causes Cd36 and insulin-mediated obesity

“…Lipid accumulation in BAT upon GC treatment has been reported previously (Ketzer et al, 2019;Luijten et al, 2019;Shen et al, 2017;Strack et al, 1995), but here we show for the first time that flattening of daily corticosterone oscillations in mice leads to lipid accumulation in BAT as well. We hypothesized that this could impact the functionality of the tissue.…”

“…With the discovery of thermogenic brown adipocytes in humans (Cypess et al, 2009;Saito et al, 2009;Van Marken Lichtenbelt et al, 2009), BAT expansion or boosting its respiratory activity has gained significant attention as a therapeutic treatment for obesity and related disorders (Betz and Enerbäck, 2015;Harms and Seale, 2013;Kusminski et al, 2016;Sidossis and Kajimura, 2015). Numerous studies showed that GC treatment in rodents can lead to accumulation of lipids in the brown fat depot (Ketzer et al, 2019;Luijten et al, 2019;Shen et al, 2017;Strack et al, 1995).…”

Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism

“…A study performed in male rats showed that the addition of CORT (0.1-0.5 mg/mL) to drinking water for 21 days induced the remodelling of BAT to WAT, resulting in an increase in whole-body adiposity. Representative BAT samples from these rats documented a reduction in UCP1 mRNA and protein expression along with an increase in WAT-specific gene expression, such as fatty acid synthase, as responsible for lipid accumulation [89]. A study of diet-induced obese mice subjected to a seven week treatment of DEX (5 mg/kg) injection every other day showed a decrease in BAT ucp1 mRNA expression and increased body fat percentage [92].…”

“…An increase in BAT thermogenic activity is one suggested therapeutic method to decrease AT lipid accumulation and prevent the development of obesity and other metabolic diseases [39]. GCs reduce the BAT-specific thermogenic and metabolic characteristics and induce whitening in BAT [89,90]. GCs also increase lipid accumulation in BAT, while decreasing non-shivering thermogenesis [40].…”