TY - JOUR
T1 - Soluble epoxide hydrolase inhibition by t-TUCB promotes brown adipogenesis and reduces serum triglycerides in diet-induced obesity
AU - Overby, Haley
AU - Yang, Yang
AU - Xu, Xinyun
AU - Graham, Katherine
AU - Hildreth, Kelsey
AU - Choi, Sue
AU - Wan, Debin
AU - Morisseau, Christophe
AU - Zeldin, Darryl C.
AU - Hammock, Bruce D.
AU - Wang, Shu
AU - Bettaieb, Ahmed
AU - Zhao, Ling
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - Brown adipogenesis
KW - Brown adipose tissue
KW - Soluble epoxide hydrolase
KW - Soluble epoxide hydrolase inhibitor
KW - T-TUCB
UR - http://www.scopus.com/inward/record.url?scp=85091994371&partnerID=8YFLogxK
U2 - 10.3390/ijms21197039
DO - 10.3390/ijms21197039
M3 - Article
C2 - 32987880
AN - SCOPUS:85091994371
SN - 1661-6596
VL - 21
SP - 1
EP - 20
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 19
M1 - 7039
ER -