Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain.
Mediators Inflamm. 2017;2017:9374563. doi: 10.1155/2017/9374563. Epub 2017 Jul 20.
Ceramide kinase (CerK) plays a critical role in the regulation of cell growth and survival and has been implicated in proinflammatory responses. In this work, we demonstrate that CerK regulates adipocyte differentiation, a process associated with obesity, which causes chronic low-grade inflammation. CerK was upregulated during differentiation of 3T3-L1 preadipocytes into mature adipocytes. Noteworthy, knockdown of CerK using specific siRNA to silence the gene encoding this kinase resulted in substantial decrease of lipid droplet formation and potent depletion in the content of triacylglycerols in the adipocytes. Additionally, CerK knockdown caused blockade of leptin secretion, an adipokine that is crucial for regulation of energy balance in the organism and that is increased in the obese state. Moreover, CerK gene silencing decreased the expression of peroxisome proliferator-activated receptor gamma (PPAR), which is considered the master regulator of adipogenesis. It can be concluded that CerK is a novel regulator of adipogenesis, an action that may have potential implications in the development of obesity, and that targeting this kinase may be beneficial for treatment of obesity-associated diseases.
神经酰胺激酶(CerK)在细胞生长和存活的调节中起着关键作用,并与促炎反应有关。在这项工作中,我们证明 CerK 调节脂肪细胞分化,这是与肥胖相关的过程,会导致慢性低度炎症。CerK 在 3T3-L1 前体脂肪细胞分化为成熟脂肪细胞的过程中上调。值得注意的是,使用特定的 siRNA 敲低 CerK,沉默编码这种激酶的基因,会导致脂滴形成大量减少,脂肪细胞中三酰基甘油含量明显减少。此外,CerK 敲低会阻断瘦素的分泌,瘦素是一种对机体能量平衡调节至关重要的脂肪细胞因子,在肥胖状态下会增加。此外,CerK 基因沉默会降低过氧化物酶体增殖物激活受体γ(PPAR)的表达,PPAR 被认为是脂肪生成的主调控因子。可以得出结论,CerK 是脂肪生成的新型调节剂,这种作用可能对肥胖的发展有潜在影响,靶向这种激酶可能有益于肥胖相关疾病的治疗。