Abstract
Indomethacin, a non-steroidal anti-inflammatory drug, has been shown to induce white adipocyte differentiation; however, its roles in brown adipocyte differentiation, and activation in brown adipose tissue (BAT) and obesity are unknown. To address this issue, we treated mouse pre-brown cells with different doses of indomethacin, and delivered indomethacin to interscapular BAT (iBAT) of obese mice using implanted osmotic pumps. Indomethacin dose-dependently increased brown adipocyte differentiation, and upregulated both mRNA and protein expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor (PPAR) gamma (γ) coactivator 1-alpha. The mechanistic study showed that indomethacin significantly activated the reporter driven by PPAR response element, indicating that indomethacin may work as a PPARγ agonist in this cell line. Consistently, indomethacin significantly decreased iBAT mass and fasting blood glucose levels in the high-fat diet induced obese (DIO) mice. Histological analysis showed that brown adipocytes of indomethacin-treated mice contained smaller lipid droplets compared to the control mice, suggesting that indomethacin alleviated the "whitening" of BAT induced by the high-fat diet. Moreover, indomethacin significantly increased UCP1 mRNA expression in the iBAT. Taken together, this study indicates that indomethacin can promote mouse brown adipocyte differentiation, and might increase brown fat and glucose oxidation capacity in DIO mice.
- The American Society for Pharmacology and Experimental Therapeutics