Ceramide kinase deficiency improves diet-induced obesity and insulin resistance

Ceramide kinase (CERK) is an enzyme that 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 by chronic, low-grade inflammation, we examined whether CERK might be 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 the adipose tissue, resulting in the suppression of inflammation in adipocytes, which might otherwise lead to obesity and diabetes.

► CERK deficiency suppressed diet-induced obesity. ► CERK deficiency suppressed diet-induced swelling of adipocytes. ► CERK deficiency suppressed diet-induced inflammation in adipose tissue. ► CERK deficiency decreased the infiltration of macrophages into adipose tissue. ► CERK deficiency impaired MCP-1/CCR2 signaling in macrophages.