147th iCeMS Seminar: Drs. Dennis E. Vance and Jean E. Vance

Prof. Dennis E. Vance

Phospholipid Methylation Has an Unexpected Role in Obesity and Insulin Resistance

Phosphatidylcholine is made in the liver via the choline pathway and via the conversion of phosphatidylethanolamine to phosphatidylcholine by 3 transmethylation reactions from AdoMet catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). PEMT is a 22.3 kDa integral transmembrane protein of the endoplasmic reticulum and mitochondria-associated membranes. The only tissue with quantitatively significant PEMT activity is liver. PEMT activity is regulated by thee concentration of substrates (phosphatidylethanolamine and AdoMet) as well as the ratio of AdoMet to AdoHcy. Studies with mice that lack PEMT have provided novel insights into the function of this enzyme. PEMT activity is required to maintain hepatic membrane integrity and for the formation of choline when dietary choline supply is limited. PEMT is required for normal secretion of very low-density lipoproteins. The lack of PEMT protects against diet-induced atherosclerosis in two mouse models. Most unexpectedly, mice that lack PEMT are also protected from diet-induced obesity and insulin resistance. However, mice lacking PEMT have increased susceptibility to diet-induced fatty liver and steatohepatitis.

Prof. Jean E. Vance

Cholesterol Transport in the Brain and Niemann-Pick C Disease

Niemann-Pick type C (NPC) disease is an inherited neurodegenerative disease in which the egress of cholesterol from late-endosomes/lysosomes is impaired. We have studied cholesterol metabolism and trafficking in primary neurons and glial cells isolated from a mouse model of NPC disease. Recent experiments indicate that a low (0.1 mM), but not a high (>1mM), dose of the cholesterol-sequestering agent, cyclodextrin, normalizes cholesterol metabolism and trafficking in these neurons and glial cells, and markedly increases lifespan of the mice. In NPC neurons and glia, the cyclodextrin mobilizes stored cholesterol from the lysosomes, thereby increasing the cholesterol content of the endoplasmic reticulum, the site at which cholesterol homeostasis is regulated. These studies support the use of low doses of cyclodextrin for treatment of NPC patients.

Lecturer	Prof Dennis E Vance School of Molecular and Systems Medicine University of Alberta, Canada Prof Jean E Vance Department of Medicine University of Alberta, Canada
Date / Time	November 15, 2013 / 16:30-18:00
Venue	2nd floor Seminar Room (#A207), iCeMS Main Building, Kyoto University Directions
Flyer	PDF (180KB)
Host	Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University
Registration	Not required.
Contact	iCeMS Ueda Group | ueda-g@icems.kyoto-u.ac.jp