第147回 アイセムスセミナー: Dennis E. Vance 教授、Jean E. Vance 教授
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.
| 講演者 | Dennis E. Vance 教授 School of Molecular and Systems Medicine University of Alberta, Canada Jean E. Vance 教授 Department of Medicine, University of Alberta, Canada |
|---|---|
| 日時 | 2013年11月15日（金）16:30-18:00 |
| 場所 | 京都大学 iCeMSコンプレックス1 本館 2階 セミナールーム (A207) アクセスマップ |
| フライヤー |  PDF (180KB) |
| 主催 | 京都大学 物質－細胞統合システム拠点（iCeMS＝アイセムス） |
| 申し込み | 不要 |
| 連絡先 | iCeMS植田グループ | ueda-g@icems.kyoto-u.ac.jp |