Title:
Recent Development of Sphingolipid Biology : general introduction and our recent works on the role of ceramide/sphingomyelin metabolism in relation to human health

Yasuyuki Igarashi
Professor
Department of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Science, Hokkaido University, JAPAN

Abstract:
In the first part of my lecture I will introduce the overview of sphingolipid biology, mainly through our own research on sphingosine1-phosphate ( S1P) cellular signaling. Additionally I will discuss membrane dynamics of sphingolipid-forming microdomain and lipid flip-flap in the membrane.
In second part, I will talk and discuss our recent work on ceramide/sphingomyelin metabolism in relation to human health. Sphingomyelin (SM) is one of the major phospholipid in plasma membrane, and has an important role for the formation of membrane lipid-microdomain. The sphingomyelin synthase (SMS) contains two isoform, SMS1 and SMS2. Although SMS1 is responsible for bulk synthesis of SM in Golgi apparatus, the role of SMS2 remains poorly understood. We first attempted to reveal the physiological function of SMS2 using knockout mice of SMS2, and found that the deficiency of SMS2 prevent high fat diet (HFD)-induced obesity and insulin resistance. We also found that sphingolipid metabolism affects exosome release from neuronal cells and we found that the exosome produced by SMS2 inhibition accelerated fibril formation and clearance of amyloid β-protein (Aβ), which is main component of the senile plaques in the brains of Alzheimer’s disease (AD). Thirdly I will talk on ceramide synthesis (especially Cers -3) and its roles in skin barrier functions

Refernces
1, Kihara A., Mitsutake S., Mizutani Y., Igarashi Y. (Review)
Metabolism and biological functions of tw o phosphorylated sphingolipids, sphingosine 1-phosphate and ceramide 1-phosphate. Prog. Lipid Res . 46(2):126-144 (2007).

2, Kihara A. Igarashi Y (Review).
Production and release of sphingosine 1-phosphate and the phosphorylated form of the immunomodulator FTY720. Biochim Biophys Acta. 1781(9):496-502 (2008).

3, Mizutani Y., Mitsutake S., kihara A., Igarashi Y. ( Review)
Ceramide biosynthesis in keratinocyte and its role in skin function Biochimie. 91(6):784-790. 2009).

4, Ohno Y. et al (Original paper)
ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis Proc. Natl. Acad. Sci. 107(43) 18439-18444 (2010).

5, Mitsutake S., Igarashi Y. et al (Original paper) Dynamics modification of sphingomyelin in lipid microdomains control development of obesity, fatty liver, and type 2 diabetes J. Biol. Chem. 286(32):28544-28555 (2011).

6, Yuyam K., Igarashi Y. et al Sphingolipid-modulated exosome secretion promotes the clearance of amyloid- b [beta] by microglia. J. Biol. Chem. revised