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Obesity (Poster Session)

(P15-056-24) Effects of Omega-3 (n-3) Epoxides on Brown Adipogenesis and Thermogenic Function

Sunday, June 30, 2024
12:45 PM – 1:45 PM CT
Location: Poster Board 55
Disclosure(s):
Haoying Wu, PhD Student: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Brown adipocytes, capable of nonshivering thermogenesis, have emerged as novel targets for increasing energy expenditure to combat obesity. Effective, safe, and practical dietary agents for enhancing brown adipogenesis have not yet been discovered. 17, 18-EEQ and 19, 20-EDP, are the predominant bioactive epoxide metabolites produced from the n-3 PUFA eicosapentaenoic acid and docosahexaenoic acid, respectively. These epoxides are metabolized to less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that when stabilized by an sEH inhibitor trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido] cyclohexyloxy} benzoic acid (t-TUCB), 17, 18-EEQ and 19, 20-EDP increased whole-body thermogenesis and improved systemic glucose and lipid metabolism in diet-induced obese mice. The study aims to investigate the direct impact of these n-3 epoxides on the development of brown adipocytes and their thermogenic function in vitro.

Methods: 17,18-EEQ or 19,20-EDP (1 or 10 μM) combined with t-TUCB (1 μM) were added during or after the differentiation of the murine brown preadipocyte to assess the epoxides’ effects on differentiation and mature adipocyte thermogenic function, respectively. Brown adipocyte differentiation was evaluated by lipid accumulation and brown marker protein expression. The thermogenic function (i.e., mitochondrial uncoupling) was evaluated by a mitochondrial stress test using an XFe24 extracellular flux analyzer.

Results: In the presence of t-TUCB, both 17,18-EEQ and 19, 20-EDP significantly increased brown adipocyte differentiation, as assessed by lipid accumulation, brown marker protein expression, and mitochondrial uncoupling. However, only 17,18-EEQ significantly increased mitochondrial uncoupling of the differentiated brown adipocytes. In addition, 17,18-EEQ and 19, 20-EDP differentially activate PPARγ in murine sEH wildtype and knockout stromal cells derived from brown adipose tissue.

Conclusions: The results demonstrate that n-3 epoxides combined with t-TUCB promote brown adipogenesis and their thermogenic function. The thermogenic potentials of n-3 epoxides warrant further exploration for obesity treatment and prevention.

Funding Sources: The work was supported by NIH.