Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
Laboratory of Molecular Biology, Azabu University School of Veterinary Medicine, Sagamihara, 252-5201, Japan.
Sci Rep. 2018 Jan 16;8(1):845. doi: 10.1038/s41598-018-19223-2.
We previously showed that brown (pre)adipocytes express Trpv1, a capsaicin receptor, and that capsaicin stimulates differentiation of brown preadipocytes in the late stages of brown adipogenesis. The present study revealed that treatment with 100 μM capsaicin stimulates brown adipogenesis by inducing endoplasmic reticulum (ER) stress. Treatment with capsaicin (100 μM) during brown adipogenesis enhanced lipid accumulation and the expression of Ucp1, a gene selectively expressed in brown adipocytes. Capsaicin treatment also caused an increase in the cytosolic calcium concentration even when extracellular calcium was removed. I-RTX, a Trpv1 inhibitor, did not modulate the increase in cytosolic calcium concentration, lipid accumulation or Ucp1 expression. Previous studies revealed that the release of calcium from the ER induces ER stress, leading to the conversion of X-box binding protein 1 (Xbp1) pre-mRNA to spliced Xbp1 (sXbp1) as well as the up-regulation of Chop expression. Capsaicin treatment increased the expression of sXbp1 and Chop in brown preadipocytes and did not enhance lipid accumulation or Ucp1 expression in Xbp1 knockdown cells. The present results describe a novel mechanism of brown adipogenesis regulation via ER stress that is induced by a supra-pharmacological concentration of capsaicin.
我们之前曾表明，棕色（前）脂肪细胞表达辣椒素受体 TRPV1，并且辣椒素刺激棕色前体脂肪细胞在棕色脂肪生成的后期分化。本研究表明，用 100μM 辣椒素处理通过诱导内质网 (ER) 应激来刺激棕色脂肪生成。在棕色脂肪生成过程中用辣椒素（100μM）处理会增强脂质积累和 Ucp1 的表达，Ucp1 是一种选择性在棕色脂肪细胞中表达的基因。辣椒素处理甚至在去除细胞外钙时也会引起细胞浆钙离子浓度增加。TRPV1 抑制剂 I-RTX 不会调节细胞浆钙离子浓度、脂质积累或 Ucp1 表达的增加。先前的研究表明，内质网钙的释放会引发内质网应激，导致 X 盒结合蛋白 1（Xbp1）前体 mRNA 向剪接 Xbp1（sXbp1）转化，并上调 Chop 表达。辣椒素处理增加了棕色前体脂肪细胞中 sXbp1 和 Chop 的表达，但在 Xbp1 敲低细胞中不会增强脂质积累或 Ucp1 表达。本研究结果描述了一种通过内质网应激诱导的、超药理学浓度辣椒素调控棕色脂肪生成的新机制。
