Novel method of measuring activities of enzymes involved in lipid metabolism

• Project/Area Number: 20590560
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kanazawa University
• Principal Investigator: KOBAYASHI Junji Kanazawa University, 医学系研究科, 特任教授 (60302577)
• Co-Investigator(Kenkyū-buntansha): NOHARA Atsushi 金沢大学, 医学系研究科, 特任助教 (50313648)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: LPL / HTGL / ANGPTL3 / 肝性リパーゼ / 内臓脂肪 / インスリン抵抗性 / リポ蛋白リパーゼ / sdLDL / メタボリックシンドローム / 低HDL

Research Abstract

We have established a simple and reliable system for measuring LPL and HTGL activities in post-heparin plasma and investigated clinical significance of measuring those activities. LPL activities showed inverse relations with TG, RLP-TG and sdLDL and positive relations with HDL-C but had no relation with ANGPTL3. HTGL activities showed no relation with TG, RLP-TG and sdLDL but had inverse relations with HDL-C and ANGPTL3. In vitro experiment showed that ANGPTL3 did not inhibit HTGL activities at all, suggesting unidentified molecule may regulate ANGPTL3 and HTGL each other in opposite directions.

Research Products

• [Journal Article] 原発性脂質異常症の分子病態 (2011)
  • Author(s): 小林淳二, 野口徹, 野原淳, 馬渕宏
  • Journal Title: Annual Review糖尿病代謝内分泌 Pages: 127-133
• [Journal Article] メタボリックシンドロームの薬物療法,スタチン系薬 (2011)
  • Author(s): 小林淳二
  • Journal Title: 日本臨床 69巻 Pages: 609-613
• [Journal Article] Comparison of losartan versus ramipril on several adipocytokines and vascular remodeling biomarkers (2011)
  • Author(s): Kobayashi j, Noguchi T, Nohara A, Mabuchi H.
  • Journal Title: Hypertens Res Volume: 34 Pages: 52-54
  • Peer Reviewed
• [Journal Article] Association of angiopoietin-like protein3 (ANGPTL3) with HTGL and LPL activities in human plasma. (2010)
  • Author(s): Nakajima, K., Kobayashi J.
  • Journal Title: Ann Clin Biochem 47 Pages: 423-431
  • Peer Reviewed
• [Journal Article] 高HDLコレステロール血症へどのように対応するか (2010)
  • Author(s): 稲津明広, 小林淳二
  • Journal Title: Medical Practice 27巻 Pages: 478-481
• [Journal Article] Impacts of visceral adipose tissue and subcutaneous adipose tissue on metabolic risk factors in middle-aged Japanese. (2010)
  • Author(s): Oka, R., Kobayashi J., Yamagishi, M.
  • Journal Title: Obesity (Silver Spring) 18 Pages: 153-160
  • Peer Reviewed
• [Journal Article] インスリン抵抗性のマーカー (2010)
  • Author(s): 小林淳二
  • Journal Title: The LIPID 21 Pages: 27-31
• [Journal Article] Association of angiopoietin-like protein3 (ANGPTL3) with HTGL and LPL activities in human plasma (2010)
  • Author(s): Nakajima K, Kobayashi J, (以下7名)
  • Journal Title: Ann Clin Biochem Volume: 47 Pages: 423-431
  • Peer Reviewed
• [Journal Article] The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation (2010)
  • Author(s): Noguchi T,(以下6名,8番目) Kobayashi, J, Mabuchi H.
  • Journal Title: Atherosclerosis Volume: 210 Pages: 166-172
  • Peer Reviewed
• [Journal Article] Difference between Fasting and Nonfasting Triglyceridemia ; the Influence of Waist Circumference. (2009)
  • Author(s): Oka, R., Kobayashi J.
  • Journal Title: J Atheroscler Thromb 16 Pages: 633-640
  • NAID: 120006338362
  • Peer Reviewed
• [Journal Article] Apolipoprotein B gene mutations and fatty liver in Japanese hypobetalipoproteinemia. (2009)
  • Author(s): Katsuda, S., Kobayashi J., Michishita, I., 馬渕宏, Yamagishi, M.
  • Journal Title: Clin Chim Acta 399 Pages: 64-68
  • Peer Reviewed
• [Journal Article] A Novel Method for Determining Functional LDL Receptor Activity in Familial Hypercholesterolemia : Application of the CD3/CD28 Assay in Lymphocytes. (2009)
  • Author(s): Tada, H., Kobayashi J., Yachie, A., 馬渕宏, Yamagishi, M.
  • Journal Title: Clin Chim Acta 400 Pages: 42-47
  • Peer Reviewed
• [Journal Article] Comparison of waist circumference with body mass index for predicting abdominal adipose tissue. (2009)
  • Author(s): Oka, R., Kobayashi J.
  • Journal Title: Diabetes Res Clin Pract 83 Pages: 100-105
  • Peer Reviewed
• [Journal Article] Retinoid X receptor heterodimer variants and cardiovascular risk factors. (2009)
  • Author(s): 野原淳, 小林淳二, 馬渕宏
  • Journal Title: J Atheroscler Thromb 16 Pages: 303-318
  • NAID: 10025765899
  • Peer Reviewed
• [Journal Article] Formation of preβ1-HDL during lipolysis of triglyceride-rich lipoprotein. (2009)
  • Author(s): Miyazaki, O., Kobayashi J.
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 55-59
  • Peer Reviewed
• [Journal Article] Development of Assay Methods for Lipoprotein Lipase and Hepatic Lipase (Activity, Mass and Activity). (2009)
  • Author(s): Kobayashi J., Imamura S., Sakasegawa Nakajima, K., Mabuchi H.
  • Journal Title: The Fats of Life. XXIII Pages: 18-21
• [Journal Article] 肝性リパーゼ脂質検査アップデート (2009)
  • Author(s): 小林淳二, 今村茂行, 酒瀬川信一, 野口徹, 野原淳, 馬渕宏
  • Journal Title: Medical Technology 37巻 Pages: 149-153
• [Journal Article] A deficiency of cholesteryl ester transfer protein whose serum remnant-like particle.(RLP)-triglyceride significantly increased, but RLP-Cholesterol did not after an oral fat load (2009)
  • Author(s): Ai M, Tanaka A, Shimokado K, Ohtani R, Inazu A, Kobayashi J, Mabuchi H, Nakano T, Nakajima K
  • Journal Title: Ann Clin Bioch 46 Pages: 457-463
  • Peer Reviewed
• [Journal Article] Expression of human apoAII in transgenic rabbits leads to dyslipidemia. A new model for combined hyperlipidemia. (2009)
  • Author(s): Koike T, Kitajima S, Yu Y, Li Y, Nishijima K, Liu E, Sun H, Waqar AB, Shibata N, Inoue T, Wang Y, Zhang B, Kobayashi J, Morimoto M, Saku K, Watanabe T, Fan J.
  • Journal Title: Arterioscler Thromb Vasc Biol 29 Pages: 2047-2053
  • Peer Reviewed
• [Journal Article] Development of Assay Methods for Lipoprotein Lipase and Hepatic Lipase (Activity, Mass and Activity) (2009)
  • Author(s): Kobayashi J, Imamura S, Sakasegawa S, Nakajima K, Mabuchi H
  • Journal Title: The Fats of Life. Volume XXIII XXIII Pages: 18-21
• [Journal Article] 肝性リパーゼ 脂質検査アップデート (2009)
  • Author(s): 小林淳二, 今村茂行, 酒瀬川信一, 野口徹, 野原淳, 馬渕宏
  • Journal Title: Medical Technology 37 Pages: 149-153
• [Journal Article] Postprandial triglyceridemia in men with impaired fating glucose, impaired glucose tolerance and diabetes. (2008)
  • Author(s): Oka, R., Kobayashi J.
  • Journal Title: Diabet Med 25 Pages: 1008-1010
  • Peer Reviewed
• [Journal Article] A novel method for measuring human lipoprotein lipase and hepatic lipase activities in post-heparin plasma. (2008)
  • Author(s): 今村茂行, 小林淳二
  • Journal Title: J Lipid Res 49 Pages: 1431-1437
  • Peer Reviewed
• [Journal Article] A novel method for measuring human lipoprotein lipase and hepatic lipase activities in post-heparin plasma. (2008)
  • Author(s): Imamura S, Kobayashi J, Nakajima K, Sakasegawa S, Nohara A, Noguchi T, Kawashiri M, Inazu A, Deeb SS, Mabuchi H, Brunzell JD
  • Journal Title: Journal of Lipid Research 49 Pages: 1431-1437
  • Peer Reviewed
• [Journal Article] Impact of bezafibrate and atorvastatin on lipoprotein subclass in patients with type III hyperlipoproteinemia : Result from a crossover study.
  • Author(s): Kawashiri, M., Kobayashi J.
  • Journal Title: Clin Chim Acta in press
  • Peer Reviewed
• [Journal Article] Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus : Results from a crossover study.
  • Author(s): 野口徹, 小林淳二
  • Journal Title: Atherosclerosis. in press
  • Peer Reviewed
• [Presentation] Angiopoietin-like protein3とリポ蛋白リパーゼ活性、肝性リパーゼ活性との相関性 (2010)
  • Author(s): 小林淳二, 中嶋克行, 野原淳, 馬渕宏
  • Organizer: 第31回日本肥満学会総会
  • Place of Presentation: 前橋テルサ(群馬県)
  • Year and Date: 2010-10-01
• [Presentation] Angiopoietin-like protein3とLPL活性、HTGL活性との相関性 (2010)
  • Author(s): 小林淳二、中嶋克行、野原淳、馬渕宏
  • Organizer: 第31回日本肥満学会総会
  • Place of Presentation: 前橋テレサ(群馬県)
  • Year and Date: 2010-10-01
• [Presentation] Effect of Licorice flavonpoid oil on plasma lipids in subjects with abdominal obesity. (2010)
  • Author(s): 小林淳二, 大家理恵, 野原淳, et al.
  • Organizer: 第42回日本動脈硬化学会総会
  • Place of Presentation: 長良川国際会議場(岐阜県)
  • Year and Date: 2010-07-15
• [Presentation] Association of ANGPTL3 with elevated HDL-C and decreased HTGL activity. (2010)
  • Author(s): 中嶋克行, 小林淳二, 馬渕宏
  • Organizer: The 6th International Atherosclerosis Society Sponsored Workshop on High Density Lipoproteins
  • Place of Presentation: Whistler Canada (Canada)
  • Year and Date: 2010-05-17
• [Presentation] Association of ANGPTL3 with elevated HDL-C and decreased HTGL activity (2010)
  • Author(s): Nakajima K, Kobayashi J, Mabuchi H.
  • Organizer: The 6th International Atherosclerosis Society Sponsored Workshop on High Density Lipoproteins
  • Place of Presentation: Westin Whistler (British Columbia) Canada
• [Presentation] 脂質異常者における肝性リパーゼと血清脂質との関係 (2009)
  • Author(s): 小林淳二, 今村茂行, 大家理恵, 野原淳, 川尻剛照、馬渕宏
  • Organizer: 第30回日本肥満学会総会
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2009-10-09
• [Presentation] 食後脂質異常と動脈硬化性疾患 (2009)
  • Author(s): 小林淳二, 大家理恵
  • Organizer: 第41回日本動脈硬化学総会
  • Place of Presentation: 海峡メッセ下関(山口県)
  • Year and Date: 2009-07-18
• [Presentation] Formation of pre β1-HDL during lipolysis of triglyceride-rich lipoprotein (2009)
  • Author(s): Kobayashi J., Miyazaki, O., Fukamachi, I., et al.
  • Organizer: XV international symposium on Atherosclerosis
  • Place of Presentation: John B.Hynes Veterans Memorial Convention Center (USA)
  • Year and Date: 2009-06-15
• [Presentation] 新たなリポ蛋白リパーゼ(LPL)活性、肝性リパーゼ(HL)活性測定法の確立 (2008)
  • Author(s): 小林淳二, 今村茂行, 中嶋克行
  • Organizer: 第40回日本動脈硬化学会総会
  • Place of Presentation: つくば国際会議場(茨城県)
  • Year and Date: 2008-07-10
• [Presentation] 新たなリポ蛋白リパーゼ(LPL)活性、肝性リパーゼ (HL) 活性測定法の確立 (2008)
  • Author(s): 小林淳二, 今村茂行, 中嶋克行, 野原淳, 川尻剛照, 植田成, 稲津明広, 山岸正和, 馬渕宏
  • Organizer: 第40回日本動脈硬イヒ学会総会
  • Place of Presentation: つくば市
  • Year and Date: 2008-07-10
• [Presentation] 新たなリポ蛋白リパーゼ(LPO)活性、肝性リパーゼ(HO活性測定法の確立 (2008)
  • Author(s): 小林淳二, 今村茂行, 中嶋克行, 野原淳, 川尻剛照, 小泉順二, 山岸正和, 馬渕宏, Brunzell JD
  • Organizer: 第51回日本糖尿病学会総会
  • Place of Presentation: 東京