Endocrine Abstracts

White adipose tissue (WAT) stores excess energy as triglycerides, while brown adipose tissue (BAT) dissipates energy through heat, acting as a defence against cold and obesity and as a positive regulator of metabolic functions. BAT thermogenic functions are mainly induced by mitochondrial uncoupling protein-1 (UCP-1), which induces uptake of lipids and glucose to sustain oxidation and thermogenesis in both brown and beige adipocytes. Beige/brite adipocytes arise in WAT depots and morphologically and functionally resemble to brown adipocytes. The glucocorticoid receptor (GR) agonist dexamethasone plays an important role in energy homeostasis, regulation of insulin sensitivity, lipid metabolism and adipose tissue distribution. Indeed, in vivo studies suggest that Dex increases the effects on UCP-1 mRNA expression in BAT. However, the role of Dex in adipose browning and BAT function is yet not fully known. Thus, we aimed to assess the role of Dex on browning of white adipocytes and brown adipocyte thermogenic functions. 3T3-L1 murine preadipocytes and human mesenchymal stem cells (hMSCs), isolated from bariatric surgery of lean subcutaneous and visceral adipose tissues, were differentiated into white adipocytes for 9 and 21 days respectively. Browning was induced for 72 h with rosiglitazone (Rosi) and insulin, in the presence or absence of Dex. Our results showed that in 3T3-L1 adipocytes Dex increased both mRNA and protein expression of BAT markers UCP-1, PRDM16, and PGC-1α. Moreover, the GR antagonist RU486 completely blocked Dex-induced mRNA expression of Ucp-1, indicating the involvement of GR on these effects. Dex also strongly enhanced the mRNA expression of the beige markers transmembrane protein 26 (TMEM26) and sirtuin 1(SIRT1), while inhibited the WAT marker C/ebpα. Interestingly, oil red O staining revealed that Dex increased the number of small lipid droplets and enhanced Iso-induced lipolysis, promoting the expression levels of adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Furthermore, Dex enhanced mitochondrial biogenesis, determined by staining with MitoTracker dye, increased the expression of the fat oxidation marker CPT1, and modulated the oxygen consumption rate (OCR), assessed by Seahorse analysis, in transdifferentiated 3T3-L1 adipocytes. Finally, Dex increased the mRNA levels of browning genes in transdifferentiated adipocytes obtained from hMSCs of both subcutaneous and visceral human adipose tissues. Overall, these findings indicate that Dex enhances the differentiation of 3T3-L1 and human white adipocytes into beige adipocytes, by regulating the expression of genes characteristics of browning and increasing beige thermogenic functions.