Soluble Epoxide Hydrolase Inhibition by t-TUCB Promotes Brown Adipogenesis and Reduces Serum Triglycerides in Diet-Induced Obesity.
Brown adipose tissue (BAT) is an important target for obesity treatment and prevention. Soluble epoxide hydrolase (sEH) converts bioactive epoxy fatty acids (EpFAs) into less active diols. sEH inhibitors (sEHI) are beneficial in many chronic diseases by stabilizing EpFAs. However, roles of sEH and sEHI in brown adipogenesis and BAT activity in treating diet-induced obesity (DIO) have not been reported. sEH expression was studied in in vitro models of brown adipogenesis and the fat tissues of DIO mice. The effects of the sEHI, trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy-benzoic acid (t-TUCB), were studied in vitro and in the obese mice via mini osmotic pump delivery. sEH expression was increased in brown adipogenesis and the BAT of the DIO mice. t-TUCB promoted brown adipogenesis in vitro. Although t-TCUB did not change body weight, fat pad weight, or glucose and insulin tolerance in the obese mice, it decreased serum triglycerides and increased protein expression of genes important for lipid metabolism in the BAT. Our results suggest that sEH may play a critical role in brown adipogenesis, and sEHI may be beneficial in improving BAT protein expression involved in lipid metabolism. Further studies using the sEHI combined with EpFA generating diets for obesity treatment and prevention are warranted.
['Overby|Haley|H|', 'Yang|Yang|Y|', 'Xu|Xinyun|X|', 'Graham|Katherine|K|', 'Hildreth|Kelsey|K|', 'Choi|Sue|S|', 'Wan|Debin|D|', 'Morisseau|Christophe|C|', 'Zeldin|Darryl C|DC|0000-0002-2087-7307', 'Hammock|Bruce D|BD|', 'Wang|Shu|S|', 'Bettaieb|Ahmed|A|', 'Zhao|Ling|L|0000-0002-8297-7039']
D052437:Adipocytes, Brown D050156:Adipogenesis D002001:Adipose Tissue, Brown D000818:Animals D001565:Benzoates D002460:Cell Line D004791:Enzyme Inhibitors D004851:Epoxide Hydrolases D006801:Humans D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D009765:Obesity D010671:Phenylurea Compounds D014280:Triglycerides
soluble epoxide hydrolase t-TUCB brown adipogenesis brown adipose tissue soluble epoxide hydrolase inhibitor