(P03-084-23) Effects of A 17, 18-EEQ Analog on Brown Adipogenesis and Browning

Objectives: Excess white adipose tissue (WAT) is a hallmark of obesity, whereas brown adipose tissue (BAT) contributes to energy expenditure through non-shivering thermogenesis. It has recently been reported that a browning process in which WAT can be induced to become beige adipose tissue with a resemblance to BAT. Functional BAT, including brown and beige adipose tissue, has become the target to increase energy expenditure through uncoupling protein (UCP1)-mediated thermogenesis. We recently reported that 17,18-epoxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (17,18-EEQ), a metabolite from eicosapentaenoic acid (an omega-3 polyunsaturated fatty acid), when stabilized by a pharmacologic inhibitor of soluble epoxide hydrolase (an enzyme that metabolizes 17,18-EEQ), efficiently promoted thermogenesis and increased energy expenditure in mice. However, 17,18-EEQ is metabolically labile; therefore, its beneficial effects in combating obesity are limited. The aim of the study was to investigate the effects of a structurally stable 17,18-EEQ analog on brown and beige adipocyte formation in mouse and human cell models.

Methods: Brown pre-adipocyte cell lines from mice and human origins and human primary stromal cells derived from WAT were treated with increasing doses of the 17,18-EEQ analog (5, 10, 20, 50 micromolar) during the differentiation process. The degree of cell differentiation was evaluated by Oil-red-O staining, protein expression of brown marker genes UCP1 and peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), and mitochondrial respiration and uncoupling.

Results: 17,18-EEQ analog significantly increased lipid accumulation, brown marker protein expression, and mitochondrial respiration and uncoupling in mice brown adipocytes. Moreover, the 17,18-EEQ analog also promoted human brown and beige adipocyte formation, as evidenced by cell morphology and increased UCP1 and PGC1α expression.

Conclusions: We conclude that the 17,18-EEQ analog promotes the formation of brown and beige adipocytes of mice and human origins. Therefore, it may be beneficial in human obesity treatment and prevention. Further studies of the effect of the analog on body weight gain, energy expenditure, and metabolic health in vivo are warranted.

Funding Sources: The work was supported by NIH.