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.
Highlights
Brown adipose tissue (BAT) has recently emerged as a novel target for obesity treatment/prevention [1,2,3]
SEH mRNA and protein expression were examined during murine brown adipogenesis in vitro. mRNA expression of Soluble epoxide hydrolase (sEH) encoding Ephx2 was time-dependently increased, along with brown marker peroxisome proliferator-activated receptor gamma (Pparγ), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α), PR domain containing 16 (Prdm16), and Ucp1 during differentiation (Figure 1A)
T-TUCB treatment via mini osmotic pump delivery decreased serum TG levels, which was accompanied by higher lipolytic protein expression, such as PLIN, in the interscapular BAT (iBAT)
Summary
Brown adipose tissue (BAT) has recently emerged as a novel target for obesity treatment/prevention [1,2,3]. In contrast to white adipose tissue (WAT), BAT is responsible for non-shivering thermogenesis through uncoupling ATP synthesis from respiration via uncoupling protein 1 (UCP1), leading to dissipation of energy as heat [1]. Using positron emission tomography/computed tomography (PET/CT) imaging, it was recently discovered that adult humans do have a significant amount of functional BAT [4,5,6,7]. These depots are either classical brown or beige fat [8,9,10]. Novel effective strategies are needed for obesity treatment and prevention
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