Prednisone stimulates white adipocyte browning via β3-AR/p38 MAPK/ERK signaling pathway

Aims: Prednisone is a corticosteroid-derived drug which is widely used for its role in immunosuppression and treatment of lung disorders. The current study reports, for the first time, the critical role of prednisone in the induction of white fat browning, thereby promoting thermogenic effect in cultured white adipocytes. Main methods: The fat-browning activity of prednisone was evaluated in 3T3-L1 cells by quantitative real-time PCR, immunoblot analysis, immunofluorescence, and molecular docking techniques. Key findings: Exposure to prednisone stimulated browning in 3T3-L1 white adipocytes by increasing the expressions of core fat browning marker proteins (UCP1, PGC-1 alpha and PRDM16) as well as beige-specific genes (Cd137, Cidea, Cited1, and Tbx1) via ATF2 and CREB activation mediated by p38 MAPK and ERK signaling, respectively. Prednisone exposure also resulted in the robust activation of lipolytic and fatty acid oxidation marker proteins, thereby increasing mitochondrial biogenesis. In addition, prednisone treatment resulted in reduced expression levels of adipogenic transcription factors while elevating SIRT1, as well as attenuation of lipogenesis and lipid droplets formation. Furthermore, molecular docking and mechanistic studies demonstrated the recruitment of beige fat by prednisone via the beta 3-AR/p38 MAPK/ERK signaling pathway. Significance: Taken together, these results indicate the unique role of prednisone as a fat-browning stimulant, and demonstrate its therapeutic potential in the treatment of obesity by enhancing thermogenesis.