(P25-037-20) Cytochrome P450 Epoxygenase Cyp2j13 Regulates Murine Brown Adipogenesis

Objectives: Brown adipocytes have emerged as novel targets for obesity treatment and prevention.  Cytochrome P450 (CYP) epoxygenases, primarily CYP2J and CYP2C isoforms, produce epoxy fatty acids (EpFAs), which have been suggested to play important roles in the regulation of white adipogenesis and obesity. However, the roles of CYP epoxygenases in brown adipogenesis remain unexplored. In this study, we sought to characterize mRNA expression patterns of Cyp2j and 2c subfamily members during adipogenesis of human and murine brown adipocytes and in obese mice and investigate the impact of modulating the expression of Cyp2j13 on brown adipogenesis.

Methods: The mRNA expression of various Cyp2j and Cyp2c isoforms were examined throughout murine and human brown adipocyte differentiation and in the brown adipose tissue (BAT) of diet-induced obese and control mice. To induce epoxygenase overexpression, stable transfection of murine brown preadipocytes with either Cyp2j13 or a vector control was performed. Protein and mRNA expression of Cyp2j13 and brown marker genes were analyzed.

Results: Expression of murine Cyp2j isoforms Cyp2j6, Cyp2j8, Cyp2j9, and Cyp2j13, and the human isoform CYP2J2 consistently decreased throughout brown adipocyte differentiation, while expression of Cyp2c isoforms did not elicit consistent patterns. Moreover, Cyp2j expression in BAT was enhanced in diet-induced obese mice compared to the controls. Due to its high relative abundance and significance, Cyp2j13 was selected for further investigation. Overexpression of Cyp2j13 significantly suppressed murine brown adipocyte differentiation as evaluated by lipid accumulation and brown marker gene UCP1 expression.

Conclusions: Our results suggest that CYP epoxygenases may play important roles in brown adipogenesis. Cyp2j13, in particular, may be a novel target for brown adipogenesis, and consequently, for obesity treatment and prevention. Further studies using CYP2J inhibitors and Cyp2j13 knockdown are warranted.

Funding Sources: The work was supported by NIH 1R15DK114790-01A1 (to L.Z.), K99DK100736 and R00DK100736 (to A.B.).