Ceramide kinase deficiency improves diet-induced obesity and insulin resistance

FEBS Lett. 2012 May 7;586(9):1300-5. doi: 10.1016/j.febslet.2012.03.032. Epub 2012 Mar 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Body Weight
  • Chemokine CCL2 / metabolism
  • Diabetes Mellitus / enzymology
  • Diet, High-Fat / adverse effects*
  • Glucose Tolerance Test
  • Insulin Resistance*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Obesity / enzymology*
  • Obesity / etiology*
  • Obesity / metabolism
  • Obesity / pathology
  • Phosphotransferases (Alcohol Group Acceptor) / deficiency*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Receptors, CCR2 / metabolism
  • Signal Transduction

Substances

  • Ccl2 protein, mouse
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Receptors, CCR2
  • Phosphotransferases (Alcohol Group Acceptor)
  • ceramide kinase