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

2013 Fiscal Year Final Research Report

• Project/Area Number: 23780344
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied molecular and cellular biology
• Research Institution: Saga University (2013); Hokkaido University (2011-2012)
• Principal Investigator: MITSUTAKE Susumu 佐賀大学, 農学部, 准教授 (10344475)
• Project Period (FY): 2011 – 2013
• Keywords: ceramide / ceramide kinase / ceraide 1-phosphate / MCP-1 / obesity / diabetes

Research Abstract

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.

Research Products

• [Journal Article] Oral administration of phytosphingosine improves high-fat diet-induced glucose intolerance Bioscience (2013)
  • Author(s): Murakami, S. Mitsutake, N. Kobayashi, J. Matsuda, A. Suzuki, T. Shigyo, Y. Igarashi
  • Journal Title: Biotechnology, and Biochemistry Volume: 77 Pages: 194-197
  • Peer Reviewed
• [Journal Article] A sensitive cell-based method to screen for selective inhibitors of SMS1 or SMS2 using HPLC and a fluorescent substrate (2012)
  • Author(s): K. Zama, S. Mitsutake, K. Watanabe, T. Okazaki, and Y. Igarashi
  • Journal Title: Chemistry and Physics of Lipids Volume: 165 Pages: 760-768
• [Journal Article] Ceramide kinase deficiency improve diet-induced obesity and insulin resistance (2012)
  • Author(s): S. Mitsutake, T. Date, H. Yokota, M. Sugiura, T. Kohama, Y. Igarashi
  • Journal Title: FEBS Letters Volume: 586 Pages: 1300-1305
  • Peer Reviewed
• [Journal Article] Dynamic modification of sphingomyelin in lipid microdomains controls development of obesity, fatty liver, and type 2 diabetes (2011)
  • Author(s): S. Mitsutake, K. Zama, H. Yokota, T. Yoshida, M. Tanaka, M. Mitsui, M. Ikawa, M. Okabe, Y. Tanaka, T. Yamashita, H. Takemoto, T. Okazaki, K. Watanabe, and Y. Igarashi
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 28544-28555
  • Peer Reviewed
• [Presentation] Glycolipid & Sphingolipid Biology (2012)
  • Author(s): "SMS2 is implicated as a novel regulator of lipid microdomain structure and function"Mitsutake, K. Zama, T. Yoshida, H. Takemoto, T. Okazaki, Y. Igarashi
  • Organizer: 2012 Gordon Research Conferences
  • Place of Presentation: Lucca, Italy(Selected speaker)
  • Year and Date: 20120422-27