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J Pharmacol Exp Ther. 2018 Jun;365(3):467-475. doi: 10.1124/jpet.117.246256. Epub 2018 Mar 22.

Indomethacin Enhances Brown Fat Activity.

Author information

1
Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas (L.H., S.S., S.W.); Department of Nutrition (J.K., L.Z.), and Research Computing Support (X.S.), University of Tennessee, Knoxville, Tennessee; Nutrition Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts (D.W.); and Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, Davis, California (S.D.K., C.M., B.D.H.).
2
Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas (L.H., S.S., S.W.); Department of Nutrition (J.K., L.Z.), and Research Computing Support (X.S.), University of Tennessee, Knoxville, Tennessee; Nutrition Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts (D.W.); and Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, Davis, California (S.D.K., C.M., B.D.H.) shu.wang@ttu.edu ling.zhao@utk.edu.

Abstract

Indomethacin, a nonsteroidal 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 brown preadipocytes with different doses of indomethacin, and delivered indomethacin to interscapular BAT (iBAT) of obese mice using implanted osmotic pumps. Indomethacin dose dependently increased brown preadipocyte differentiation and upregulated both mRNA and protein expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor (PPAR) γ coactivator 1-alpha. The mechanistic study showed that indomethacin significantly activated the reporter driven by the 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 high-fat diet-induced obesity (DIO) mice. Histologic analysis showed that brown adipocytes of indomethacin-treated mice contained smaller lipid droplets compared with control mice, suggesting that indomethacin alleviated the whitening of BAT induced by the high-fat diet. Moreover, indomethacin significantly increased UCP1 mRNA expression in 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.

PMID:
29567865
PMCID:
PMC5931432
[Available on 2019-06-01]
DOI:
10.1124/jpet.117.246256

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