BKCa 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 (BKCa channels) are expressed in adipose tissue and adipocyte-specific BKCa deficiency resists obesity in mice, but the role of BKCa channels in lipid deposition and the underlying mechanisms have not been elucidated. In the present study, we generated BKCa 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 BKCa 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 BKCa KO rats. Furthermore, we found that the insulin-induced increase of intracellular calcium resulting from extracellular calcium influx was significantly impaired in BKCa KO adipocytes. Finally, insulin activated BKCa currents through PI3K, which was independent of Akt and intracellular calcium. The results of this study suggested that BKCa channels participate in the insulin signaling pathway and promote TG deposition by increasing extracellular calcium influx in adipocytes.

Exercise improved lipid metabolism and insulin sensitivity in rats fed a high-fat diet by regulating glucose transporter 4 (GLUT4) and musclin expression

This study aimed to evaluate the effects of exercise training on triglyceride deposition and the expression of musclin and glucose transporter 4 (GLUT4) in a rat model of insulin resistance. Thirty male Sprague-Dawley rats (8 weeks old, weight 160±10 g) were fed a high-fat diet (40% calories from fat) and randomly divided into high-fat control group and swimming intervention group. Rats fed with standard food served as normal control. We found that 8-week swimming intervention significantly decreased body weight (from 516.23±46.27 to 455.43±32.55 g) and visceral fat content (from 39.36±2.50 to 33.02±2.24 g) but increased insulin sensitivity index of the rats fed with a high-fat diet. Moreover, swimming intervention improved serum levels of TG (from 1.40±0.83 to 0.58±0.26 mmol/L) and free fatty acids (from 837.80±164.25 to 556.38±144.77 μEq/L) as well as muscle triglycerides deposition (from 0.55±0.06 to 0.45±0.02 mmol/g) in rats fed a high-fat diet. Compared with rats fed a standard food, musclin expression was significantly elevated, while GLUT4 expression was decreased in the muscles of rats fed a high-fat diet. In sharp contrast, swimming intervention significantly reduced the expression of musclin and increased the expression of GLUT4 in the muscles of rats fed a high-fat diet. In conclusion, increased musclin expression may be associated with insulin resistance in skeletal muscle, and exercise training improves lipid metabolism and insulin sensitivity probably by upregulating GLUT4 and downregulating musclin.