Soluble epoxide hydrolase inhibition by t-TUCB promotes brown adipogenesis and reduces serum triglycerides in diet-induced obesity

Haley Overby, Yang Yang, Xinyun Xu, Katherine Graham, Kelsey Hildreth, Sue Choi, Debin Wan, Christophe Morisseau, Darryl C. Zeldin, Bruce D. Hammock, Shu Wang, Ahmed Bettaieb, Ling Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number7039
Pages (from-to)1-20
Number of pages20
JournalInternational journal of molecular sciences
Volume21
Issue number19
DOIs
StatePublished - Oct 1 2020
Externally publishedYes

Keywords

  • Brown adipogenesis
  • Brown adipose tissue
  • Soluble epoxide hydrolase
  • Soluble epoxide hydrolase inhibitor
  • T-TUCB

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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