Role of Cyp2j6 in Brown Adipogenesis

OBJECTIVES: Brown adipocytes are novel targets for obesity treatment and prevention. Cytochrome P-450 (CYP) epoxygenases, Cyp2j family members in particular, produce epoxy fatty acids (EpFAs), which are known to play important roles in regulating adipogenesis and obesity. However, the effects of Cyp2j6, the most abundant member of the Cyp2j family, on brown adipogenesis have not been reported. Here, we examined mRNA expression patterns of Cyp2j6 in brown vs. white adipogenesis and diet-induced obesity and investigated the impact of overexpression of Cyp2j6 on brown adipogenesis. METHODS: Cyp2j6 mRNA expression was examined in murine brown vs. white adipocyte differentiation and the brown (iBAT), epididymal (eWAT), and inguinal white adipose tissue (iWAT) of diet-induced obese mice. Moreover, murine brown pre-adipocytes were stably transfected with either Cyp2j6 or the vector control to investigate the effects of Cyp2j6 overexpression on brown adipogenesis. RESULTS: Cyp2j6 mRNA was significantly suppressed in differentiated brown adipocytes compared to brown pre-adipocytes. In contrast, Cyp2j6 mRNA was not changed in white adipocyte differentiation. Moreover, Cyp2j6 mRNA was elevated in iBAT, eWAT, and iWAT of diet-induced obese mice compared to the controls; however, only Cyp2j6 mRNA in the eWAT reached significance. Furthermore, Cyp2j6 overexpression significantly suppressed murine brown adipocyte differentiation as evaluated by lipid accumulation and brown markers’ expression. CONCLUSIONS: Our results suggest that Cyp2j6 may play an important role in brown adipogenesis. Further studies of Cyp2j6 in brown adipogenesis and BAT development in vivo are warranted. FUNDING SOURCES: The work was supported by NIH.