PDF(Pubmed)
Abstract：
Adipogenesis is one of the major mechanisms for adipose tissue expansion, during which spindle-shaped mesenchymal stem cells commit to the fate of adipocyte precursors and differentiate into round-shaped fat-laden adipocytes. Here, we investigated the lipidomic profile dynamics of ex vivo-differentiated brown and white adipocytes derived from the stromal vascular fractions of interscapular brown (iBAT) and inguinal white adipose tissues. We showed that sphingomyelin was specifically enriched in terminally differentiated brown adipocytes, but not white adipocytes. In line with this, freshly isolated adipocytes of iBAT showed higher sphingomyelin content than those of inguinal white adipose tissue. Upon cold exposure, sphingomyelin abundance in iBAT gradually decreased in parallel with reduced sphingomyelin synthase 1 protein levels. Cold-exposed animals treated with an inhibitor of sphingomyelin hydrolases failed to maintain core body temperature and showed reduced oxygen consumption and iBAT UCP1 levels. Conversely, blockade of sphingomyelin synthetic enzymes resulted in enhanced nonshivering thermogenesis, reflected by elevated body temperature and UCP1 levels. Taken together, our results uncovered a relation between sphingomyelin abundance and fine-tuning of UCP1-mediated nonshivering thermogenesis.
摘要：
脂肪生成是脂肪组织扩张的主要机制之一，在此期间，纺锤形的间充质干细胞致力于脂肪细胞前体的命运，并分化为圆形的脂肪细胞。这里,我们研究了源自肩胛骨间棕色(iBAT)和腹股沟白色脂肪组织(iWAT)的基质血管部分的离体分化棕色和白色脂肪细胞的脂质组学动力学.我们表明鞘磷脂在终末分化的棕色脂肪细胞中特异性富集，但不是白色脂肪细胞.与此相符,iBAT新鲜分离的脂肪细胞显示出比iWAT更高的鞘磷脂含量。在寒冷暴露时，随着鞘磷脂合酶1蛋白水平的降低,iBAT中的鞘磷脂丰度逐渐降低。接受鞘磷脂水解酶抑制剂治疗的冷暴露动物无法维持核心体温，并且耗氧量和iBATUCP1水平降低。相反，神经鞘磷脂合成酶的阻断导致非颤抖产热增强，反映在体温升高和UCP1水平。一起来看,我们的结果揭示了鞘磷脂丰度与UCP1介导的非颤抖产热微调之间的关系。
