Roles of BMAL1 in adipocytes

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Adipose differentiation is regulated by several transcription factors, such as a C/EBP family and PPARγ2. In this study, we have studied the roles of the BMAL1 in adipogenesis. During adipose differentiation in 3T3-L1 cells, the level of the BMAL mRNA began to increase is highly expressed in differentiated cells. In white adipose tissues isolated from C57BL/6J mice, BMALI is predominantly expressed in adipocytes fraction compared with stromal-vascular fraction. Knock down of BMAL1 mRNA expression in 3T3-L1 cells by RNAi technique allowed the cells to accumulate minimum amounts of lipid droplets in the cells. Expression of adipocytes-related genes was greatly induced in the control cells after 7 days of differentiation. Consistent with the morphological observations, a minimum amount of adipocytes-related genes was induced in the BMAL 1 knock down cells. Adenovirus-mediated expression of BMAL1 in mature adipocytes induced several genes required for lipid metabolism. These results indicated that BMAL1 play roles in adipogenesis in 3T3-L1 cells. Then. we wished to examine if BMALI has the ability to promote adipogenesis in NIH 3T3 cells, a relatively nonadipogenic cell line. NIH 3T3 cells were stably transfected with a vector expressing high levels of full length BMALI mRNA, or a control vector. To evaluate the differentiation potency of the clones, the cells were cultured to confluence and then treated with a standard differentiation-induction medium containing and PPAR γ2 ligands (troglitazone or ETYA). Overexpression of BMAL1 in NIH 3T3 cells induced significant amounts of lipids accumulation compared with the control cells. The results were also confirmed by measuring the expression of adipocyte-related genes. These results suggest that BMAL1 plays important role in the regulation of adipose differentiation.