Regulation of hepatic glucose and lipid metabolism by ER stress response

• Project/Area Number: 20790643
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Kanazawa University
• Principal Investigator: OTA Tsuguhito Kanazawa University, フロンティアサイエンス機構, 特任助教 (60397213)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 脂質代謝異常 / 脂肪肝 / 小胞体ストレス / インスリン抵抗性 / 炎症 / 脂質代謝 / 糖尿病 / 非アルコール性脂肪肝炎(NASH) / 肝臓 / インリン抵抗性

Research Abstract

Increased secretion of apolipoprotein B (apoB)-containing lipoproteins, particularly VLDL, and hepatic steatosis are characteristic concomitants of insulin resistance, the metabolic syndrome, and type 2 diabetes. Endoplasmic reticulum (ER) stress plays a central role in the development of hepatic insulin resistance and steatosis. Each fattyacid (FA), when administered for prolonged periods of time, can, at certain doses, inhibit apoB secretion. The effects of OA and PA parallel their ability to induce ER stress; PA is more potent and acts, in part, via ceramide. DHA is the most potent inhibitor but this is independent of ER stress.

Research Products

• [Journal Article] Palmitate Induces Insulin Resistance in H4IIEC3 Hepatocytes through Reactive Oxygen Species Produced by Mitochondria. (2009)
  • Author(s): Nakamura S, Takamura T, Matsuzawa-Nagata N, Takayama H, Misu H, Noda H, Nabemoto S, Kurita S, Ota T, Ando H, Miyamoto K, Kaneko S
  • Journal Title: J Biol Chem 284 Pages: 14809-14818
  • NAID: 120002829203
  • Peer Reviewed
• [Journal Article] 高脂血症・脂肪肝形成におけるERストレスの意義メタボリックシンドロームから消化器疾患に迫る (2009)
  • Author(s): 太田嗣人
  • Journal Title: 分子消化器病 6 Pages: 37-40
• [Journal Article] Palmitate Induces Insulin Resistance in H4IIEC3 Hepatocytes through Reactive Oxygen Species Produced by Mitochondria. (2009)
  • Author(s): Nakamura S, Takamura T, Matsuzawa-Nagata N, Takayama H, Misu H, Noda H, Nabemoto S, Kurita S, Ota T, et al.
  • Journal Title: J Biol Chem 284 Pages: 14809-14818
  • NAID: 120002829203
  • Peer Reviewed
• [Journal Article] Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis. (2008)
  • Author(s): Uno M, Kurita S, Misu H, Ando H, Ota T, Matsuzawa-Nagata N, Kita Y, Nabemoto S, Akahori H, Zen Y, Nakanuma Y, Kaneko S, Takamura T
  • Journal Title: Hepatology 48 Pages: 109-118
  • NAID: 120001130339
  • Peer Reviewed
• [Journal Article] Obesity upregulates genes involved in oxidative phosphorylation in livers of diabetic patients. (2008)
  • Author(s): Takamura T, Misu H, Matsuzawa-Nagata N, Sakurai M, Ota T, Shimizu A, Kurita S, Takeshita Y, Ando H, Honda M, Kaneko S
  • Journal Title: Obesity (Silver Spring) 16 Pages: 2601-2609
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects. (2008)
  • Author(s): Kurita S, Takamura T, Ota T, Matsuzawa-Nagata N, Kita Y, Uno M, Nabemoto S, Ishikura K, Misu H, Ando H, Zen Y, Nakanuma Y, Kaneko S
  • Journal Title: Eur J Pharmacol 588 Pages: 316-324
  • NAID: 120001130222
  • Peer Reviewed
• [Journal Article] Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity. (2008)
  • Author(s): Matsuzawa-Nagata N, Takamura T, Ando H, Nakamura S, Kurita S, Misu H, Ota T, Yokoyama M, Honda M, Miyamoto K, Kaneko S
  • Journal Title: Metabolism 57 Pages: 1071-1077
  • NAID: 120001130340
  • Peer Reviewed
• [Journal Article] 脂肪肝とリポトキシシティ;リポトキシシティを見直す (2008)
  • Author(s): 太田嗣人, 篁俊成
  • Journal Title: The Lipid 19 Pages: 20-26
• [Journal Article] Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis (2008)
  • Author(s): Uno M, Kurita S, Misu H, Ando H, Ota T, et.al.
  • Journal Title: Hepatology 48 Pages: 109-118
  • NAID: 120001130339
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through itspleiotropic effects (2008)
  • Author(s): Kurita S, Takamura T, Ota T, et.al.
  • Journal Title: Eur J Pharmacol 588 Pages: 316-324
  • Peer Reviewed
• [Journal Article] Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistanceand obesity (2008)
  • Author(s): Takamura T, Misu H, Matsuzawa N, Sakurai M, Ota T, et.al.
  • Journal Title: Metabolism 57 Pages: 1071-1077
  • Peer Reviewed
• [Presentation] Inhibition Of Apolipoprotein B100 Secretion By Lipid-induced Hepatic Endoplasmic Stress (2009)
  • Author(s): Ota T, Gayet C, Ginsberg HN
  • Organizer: 第41回動脈硬化学会
  • Place of Presentation: 海峡メッセ(山口)
  • Year and Date: 2009-07-17
• [Presentation] Identification of a redox-associated hepatokine that contributes to systemic insulin resistance Keystone Symposia on Molecular and Cellular Biology (2009)
  • Author(s): Takamura T, Misu H, Nagata N, Ishikura K, Ota T, Kaneko S
  • Organizer: Type 2 Diabetes and Insulin Resistance J3 352
  • Place of Presentation: USA
  • Year and Date: 2009-01-21
• [Presentation] インスリン抵抗性で生じる小胞体ストレスはapoB分泌を選択的に阻害し脂肪肝を促進する (2008)
  • Author(s): 太田嗣人, 篁俊成, 金子周一, Henry Ginsberg
  • Organizer: 第23回日本糖尿病合併症学会
  • Place of Presentation: 日本都市センター(東京)
  • Year and Date: 2008-10-03
• [Presentation] Different fatty acids inhibit apoB100 secretion by both common and unique molecularpathways (2008)
  • Author(s): Ota T. Gavet C. Ginsbera HN
  • Organizer: 2008年欧州糖尿病学会議(EASD)
  • Place of Presentation: ローマ
  • Year and Date: 2008-09-10
• [Presentation] Different fatty acids inhibit apoB100 secretion by both common and unique molecular pathways Diabetologia 51 (suppl. 1) S299 (2008)
  • Author(s): Ota T, Gayet C, Ginsberg HN
  • Organizer: Presented at the 2008 Meeting of the European Association for the Study of Diabetes (EASD)
  • Place of Presentation: Italy
  • Year and Date: 2008-09-09
• [Presentation] Ginsberg HN脂肪酸誘導性肝小胞体ストレスはapoB100分泌を選択的に阻害し肝脂肪化を促進する (2008)
  • Author(s): 太田嗣人
  • Organizer: 第51日本糖尿病学会年次学術集会
  • Place of Presentation: 東京フォーラム(東京)
  • Year and Date: 2008-05-23
• [Book] 分子消化器病2009年3月号メタボリックシンドロームから消化器疾患に迫る (2008)
  • Author(s): 太田嗣人
  • Total Pages: 6
  • Publisher: 脂質異常症・脂肪肝形成におけるERストレスの意義
• [Remarks]
  • URL: http://ota.w3.kanazawa-u.ac.jp/