Study on the role of ceramide kinase in the macrophage-function

慢性和低度炎症与肥胖的最初阶段有关。神经酰胺激酶(Cerk)是一种将神经酰胺磷酸化生成1-磷酸神经酰胺的酶。最近，有证据表明，Cerk在免疫细胞的炎症信号转导中发挥作用。由于肥胖伴随着慢性、低级别的炎症，我们使用CERK缺失的小鼠检测了CERK是否可能参与其中。我们确定Cerk缺乏抑制了饮食诱导的体重增加，并改善了葡萄糖耐量。此外，我们还证实，Cerk缺乏可减弱渗透脂肪组织的巨噬细胞中的MCP-1/CCR2信号，从而抑制脂肪中的炎症，否则可能导致肥胖和糖尿病。

Chronic and low-grade inflammation is associated with the initial steps of obesity. Ceramide kinase (CERK) is an enzyme which phosphorylates ceramide to produce ceramide 1-phosphate. Recently, evidence has emerged that CERK has a role in inflammatory signaling of immune cells. Since obesity is accompanied with chronic, low-grade inflammation, we examined whether CERK might involved using CERK-null mice. We determined that CERK deficiency suppresses diet-induced increases in body weight, and improves glucose intolerance. Furthermore, we demonstrated that CERK deficiency attenuates MCP-1/CCR2 signaling in macrophages infiltrating adipose tissue, resulting in the suppression of inflammation in adipose, which might otherwise lead to obesity and diabetes.