BK_Ca channel participates in insulin-induced lipid deposition in adipocytes by increasing intracellular calcium

Storing energy in the form of triglyceride (TG) is one of the basic functions of adipose tissue. Large-conductance calcium-activated potassium channels (BK_Ca channels) are expressed in adipose tissue and adipocyte-specific BK_Ca deficiency resists obesity in mice, but the role of BK_Ca channels in lipid deposition and the underlying mechanisms have not been elucidated. In the present study, we generated BK_Ca knockout (KO) rats and performed a transcriptome analysis of adipose tissue. We found that the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, which is important for lipid deposition, exhibited the most notable reduction among various signaling pathways in BK_Ca KO rats compared to wild-type rats. Insulin-induced TG deposition, glucose uptake, and Akt (Ser473) phosphorylation were significantly reduced in cultured adipocytes differentiated from adipose-derived stem cells of BK_Ca KO rats. Furthermore, we found that the insulin-induced increase of intracellular calcium resulting from extracellular calcium influx was significantly impaired in BK_Ca KO adipocytes. Finally, insulin activated BK_Ca currents through PI3K, which was independent of Akt and intracellular calcium. The results of this study suggested that BK_Ca channels participate in the insulin signaling pathway and promote TG deposition by increasing extracellular calcium influx in adipocytes.