Elucidation of the athlete paradox and examination of clinical application

• Project/Area Number: 15H03097
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: Juntendo University
• Principal Investigator: KAWAMORI ryuzo 順天堂大学, 医学(系)研究科(研究院), 特任教授 (00116021)
• Co-Investigator(Kenkyū-buntansha): 筧 佐織 順天堂大学, 医学(系)研究科(研究院), 特任助教 (00450560) ; 田村 好史 順天堂大学, 国際教養学部, 教授 (80420834)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: アスリートパラドクス / 骨格筋 / 骨格筋細胞内脂質 / インスリン感受性 / 運動 / アスリートパラドックス

Outline of Final Research Achievements

Skeletal muscle from exercised-trained subjects can display high insulin sensitivity, despite intramuscular lipid levels that exceed those of obese and diabetic individuals, a phenomenon described as the “athlete paradox”. However it is unknown whether exercises intensity is reflect to lipid alterations and insulin sensitivity. To clarify its mechanisms, we investigated PGC1 promoter methylation ratio and the role of exercise intensity on intramyocellular lipid level and insulin resistance. As a result, between the athlete and the control, there was a difference in the methylation rate on the PGC1 promoter. On the other hand, the composition of skeletal muscle intracellular lipid and blood lipid differed in change depending on exercise intensity. These results suggest that epigenetic regulation is one of the causes of athlete paradox and setting exercise intensity is important for prevention of metabolic syndrome.

Research Products

• [Journal Article] Long-term, but not short-term high-fat diet induces fiber composition changes and impaired contractile force in mouse fast-twitch skeletal muscle (2017)
  • Author(s): Eshima H,Tamura Y, Kakehi S, Kurebayashi N, Murayama T, Nakamura K, Kakigi R,Okada T,Sakurai T, Kawamori R, Watada H
  • Journal Title: Physiological reports Volume: 5 Issue: 7 Pages: e13250-e13250
  • DOI: 10.14814/phy2.13250
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Correlates of insulin clearance in apparently healthy non-obese Japanese men. (2017)
  • Author(s): Kaga H, Tamura Y, Takeno K, Kakehi S, Funayama T, Furukawa Y, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Giacca A, Kanazawa A, Kawamori R, Watada H.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 1462-1462
  • DOI: 10.1038/s41598-017-01469-x
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Impaired peripheral insulin sensitivity in non-obese Japanese patients with type 2 diabetes mellitus and fatty liver. (2017)
  • Author(s): Furukawa Y, Tamura Y, Takeno K, Funayama T, Kaga H, Suzuki R, Watanabe T, Kakehi S, Kanazawa A, Kawamori R, Watada H.
  • Journal Title: J Diabetes Investig. Volume: 印刷中 Issue: 3 Pages: 529-535
  • DOI: 10.1111/jdi.12731
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of Glucose Metabolism in Underweight Japanese Women. (2017)
  • Author(s): Someya Y, Tamura Y, Suzuki R, Kaga H, Kadowaki S, Sugimoto D, Kakehi S, Funayama T, Furukawa Y, Takeno K, Sato J, Kanazawa A, Kawamori R, Watada H.
  • Journal Title: J Endocr Soc. Volume: 2(3) Issue: 3 Pages: 279-289
  • DOI: 10.1210/js.2017-00418
  • Peer Reviewed
• [Journal Article] Effects of alcohol abstinence on glucose metabolism in Japanese men with elevated fasting glucose: A pilot study. (2017)
  • Author(s): Funayama T, Tamura Y, Takeno K, Kawaguchi M, Kakehi S, Watanabe T, Furukawa Y, Kaga H, Yamamoto R, Kanazawa A, Fujitani Y, Kawamori R, Watada H.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 40277-40277
  • DOI: 10.1038/srep40277
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relation Between Insulin Sensitivity and Metabolic Abnormalities in Japanese Men With BMI of 23-25 kg/m2. (2016)
  • Author(s): Takeno K, Tamura Y, Kawaguchi M, Kakehi S, Watanabe T, Funayama T, Furukawa Y, Kaga H, Yamamoto R, Kim M, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Taka H, Fujimura T, Sawada SS, Giacca A, Kanazawa A, Fujitani Y, Kawamori R, Watada H.
  • Journal Title: J Clin Endocrinol Metab Volume: 101 Pages: 3676-3684
  • Peer Reviewed
• [Journal Article] A randomized controlled trial of 130 g/day low-carbohydrate diet in type 2 diabetes with poor glycemic control. (2016)
  • Author(s): Sato J, Kanazawa A, Makita S, Hatae C, Komiya K, Shimizu T, Ikeda F, Tamura Y, Ogihara T, Mita T, Goto H, Uchida T, Miyatsuka T, Takeno K, Shimada S, Ohmura C, Watanabe T, Kobayashi K, Miura Y, Iwaoka M, Hirashima N, Fujitani Y, Watada H.
  • Journal Title: Clin Nutr Volume: 16 Issue: 4 Pages: 30169-8
  • DOI: 10.1016/j.clnu.2016.07.003
  • Peer Reviewed
• [Journal Article] Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet. (2016)
  • Author(s): Kakehi S, Tamura Y, Takeno K, Sakurai Y, Kawaguchi M, Watanabe T, Funayama T, Sato F, Ikeda S, Kanazawa A, Fujitani Y, Kawamori R, Watada H.
  • Journal Title: Am J Physiol Endocrinol Metab. Volume: 310 Issue: 1 Pages: 32-40
  • DOI: 10.1152/ajpendo.00220.2015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Efficacy and safety of 40 mg or 60 mg duloxetine in Japanese adults with diabetic neuropathic pain: Results from a randomized, 52-week, open-label study. (2016)
  • Author(s): Yasuda H, Hotta N, Kasuga M, Kashiwagi A, Kawamori R, Yamada T, Baba Y, Alev L, Nakajo K.
  • Journal Title: J Diabetes Investig Volume: 7 Issue: 1 Pages: 100-108
  • DOI: 10.1111/jdi.12361
  • Peer Reviewed
• [Journal Article] Dynamic prediction model and risk assessment chart for cardiovascular disease based on on-treatment blood pressure and baseline risk factors. (2016)
  • Author(s): Teramukai S, Okuda Y, Miyazaki S, Kawamori R, Shirayama M Teramoto T.
  • Journal Title: Hypertension Research Volume: 39 Issue: 2 Pages: 113-118
  • DOI: 10.1038/hr.2015.120
  • Peer Reviewed
• [Journal Article] Does the treatment of type 2 diabetes mellitus with the DPP -4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients? (2016)
  • Author(s): James E Foley, Vaishali Bhosekar, Kawamori R.
  • Journal Title: Vascular Health and Risk Management Volume: 12 Pages: 9-12
  • DOI: 10.2147/vhrm.s96971
  • Peer Reviewed
• [Journal Article] Effects of Pioglitazone for Secondary Stroke Prevention in Patients with Impaired Glucose Tolerance and Newly Diagnosed Diabetes: The J-SPIRIT Study (2015)
  • Author(s): Tanaka R, Yamashiro K, Okuma Y, Shimura H, Nakamura S, Ueno Y, Tanaka Y, Miyamoto N, Tomizawa Y, Nakahara T, Furukawa Y, Watada H, Kawamori R, Hattori N, Urabe T.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 22 Issue: 12 Pages: 1305-1316
  • DOI: 10.5551/jat.30007
  • NAID: 130005112370
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Replication study in a Japanese population to evaluate the association between 10 SNP loci, identified in European genome-wide association studies, and type 2 diabetes. (2015)
  • Author(s): Matsuba R,, Sakai K, Imamura M, Tanaka Y, Iwata M, Hiroshe H, Kaku K, Maegawa H, WatadaH, Tobe K, Kashiwagi A, Kawamori R, Maeda S.
  • Journal Title: Plos One Volume: 10 Issue: 5 Pages: e0126363-e0126363
  • DOI: 10.1371/journal.pone.0126363
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of Myocardial Triglyceride Accumulation Assessed on ¹H-Magnetic Resonance Spectroscopy in Apparently Healthy Japanese Subjects (2015)
  • Author(s): Sai E, Shimada K, Yokoyama T, Sato S, Nishizaki Y, Miyazaki T, Hiki M, Tamura Y, Aoki S, Watada H, Kawamori R, Daida H.
  • Journal Title: Internal Medicine Volume: 54 Issue: 4 Pages: 367-373
  • DOI: 10.2169/internalmedicine.54.3024
  • NAID: 130004903049
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Four-year evolution of insulin regimens, glycaemic control, hypoglycaemia and body weight after starting insulin therapy in type 2 diabetes across three continents. (2015)
  • Author(s): Home PD, Dain M-P, Freemantle N, Kawamori R, Pfohl M, Brette S, Pilorget V, Scherbaum WA, Vespasiani G, Vincent M, Balkau B.
  • Journal Title: Diabetes Res Clin Pract Volume: 108 Issue: 2 Pages: 350-9
  • DOI: 10.1016/j.diabres.2015.01.030
  • Peer Reviewed
• [Journal Article] The factors that affect exercise therapy for patients with type 2 diabetes in Japan: a nationwide survey. (2015)
  • Author(s): Arakawa S, Watanabe T, Sone H, Tamura Y, Kobayashi M, Kawamori R, Atsumi Y, Oshida Y, Tanaka S, Suzuki S, Makita S, Ohsawa I, Sato Yuzo.
  • Journal Title: Diabetol Int Volume: 6 Pages: 19-25
  • Peer Reviewed
• [Journal Article] Lipid and Blood Pressure Control for the Prevention of Cardiovascular Disease in Hypertensive Patients: A Subanalysis of the OMEGA Study (2015)
  • Author(s): Teramoto T, Kawamori R, Miyazaki S, Teramukai S, Sato Y, Okuda Y, Shirayama M.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 22 Issue: 1 Pages: 62-75
  • DOI: 10.5551/jat.25304
  • NAID: 130004684914
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver: A pilot study (2014)
  • Author(s): Watanabe T, Tamura Y, Kakehi S, Funayama T, Takeno K, Kawaguchi M, Yamamoto L, Sato F, Ikeda S, Taka H, Fujimura T, Fujitani Y, Kawamori R, Watada H
  • Journal Title: J Diabetes Invest Volume: Mar;6(2) Issue: 2 Pages: 164-72
  • DOI: 10.1111/jdi.12262
  • Peer Reviewed / Open Access
• [Presentation] Effects of difference in exercise intensity under the same energy consumption on the phospholipid composition in muscle (2017)
  • Author(s): Saori Kakehi, Yoshifumi Tamura, Takashi Funayama, Kageumi Takeno, Ryuzo Kawamori and Hirotaka Watada
  • Organizer: Cell symposia Exercises Metabolism
  • Int'l Joint Research
• [Presentation] Physical inactivity and high fat diet additively induce diacylglycerol accumulation and insulin resistance (2016)
  • Author(s): Saori Kakehi, Yoshifumi Tamura, Shin-ichi Ikeda, Naoko Kaga, Ryuzo Kawamori, Hirotaka Wata
  • Organizer: 76th American Diabetes Association Scientific Sessions
  • Place of Presentation: New Orleans, Louisiana
  • Year and Date: 2016-06-10
  • Int'l Joint Research
• [Presentation] 高脂肪食・不活動による骨格筋インスリン抵抗性発生メカニズム (2016)
  • Author(s): 筧 佐織
  • Organizer: 第59回日本糖尿尿病学会年次学術集会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2016-05-19
  • Invited
• [Presentation] 高脂肪・不活動による骨格筋インスリン抵抗性惹起メカニズム (2015)
  • Author(s): 筧 佐織、田村 好史、池田 真一、加賀 直子、河盛 隆造、綿田 裕孝
  • Organizer: 分子糖尿病学シンポジウム
  • Place of Presentation: 東京、千代田区、丸ビルホール&コンファレンススクエア
  • Year and Date: 2015-12-05
• [Presentation] 24時間の脚ギプス固定は、骨格筋細胞内のジアシルグリセロールを増加させ、インスリン抵抗性を惹起する (2015)
  • Author(s): 筧 佐織、田村 好史、池田 真一、河盛 隆造、綿田 裕孝
  • Organizer: 第70回体力医学会大会
  • Place of Presentation: 和歌山、和歌山市、和歌山県民文化会館
  • Year and Date: 2015-09-18
• [Presentation] Intramyocellular lipid accumulation after high-fat diet is associated with the gene expression involved in lipid metabolism in skeletal muscle of non-obese men (2015)
  • Author(s): Kakehi S, Tamura Y, Takeno K, Sakurai Y, Kawaguchi M, Watanabe T, Funayama T, Sato F, Ikeda S, Kanazawa A, Fujitani Y, Kawamori R, Watada H
  • Organizer: 2nd Congress, International Academy of Sportology.
  • Place of Presentation: 東京、文京区、順天堂大学
  • Year and Date: 2015-09-12
• [Presentation] Physical inactivity and high fat diet synergistically enhance the accumulation of intramyocellular diacylglycerol and induce insulin resistance in murine soleus muscle (2015)
  • Author(s): Kakehi S, Tamura Y, Kawamori R, Watada H
  • Organizer: Cell Symposia: Exercise Metabolism.
  • Place of Presentation: アムステルダム、オランダ
  • Year and Date: 2015-07-12
• [Presentation] 「Potential usefulness of intrahepatic lipid accumulation and liver function tests to identify insulin resistance phenotype in non-obese type 2 diabetes.」 (2015)
  • Author(s): Y. Furukawa, Y. Tamura, K. Takeno, T. Funayama, R. Suzuki, H. Kaga, T. Watanabe, Y. Someya, Y. Fujitani, R. Kawamori, H. Watada
  • Organizer: American Diabetes Association 75th scientific sessions
  • Place of Presentation: ボストン、アメリカ合衆国
  • Year and Date: 2015-06-05
• [Presentation] Mechanisums of insulin resistance after 24hours physical inactivity in murine soleus muscle (2015)
  • Author(s): Kakehi S, Tamura Y, Ikeda S, Kawamori R, Watada H
  • Organizer: 62nd Annual Meeting of American College of Sports Medicine.
  • Place of Presentation: サンディエゴ、アメリカ合衆国
  • Year and Date: 2015-05-26