Clinical significance and mechanism of fat load susceptibility

• Project/Area Number: 18H03196
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Juntendo University
• Principal Investigator: Tamura Yoshifumi 順天堂大学, 国際教養学部, 教授 (80420834)
• 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) ; 加賀 英義 順天堂大学, 医学部, 助教 (90814757)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: インスリン抵抗性 / 異所性脂肪 / 高脂肪食 / 脂肪肝 / 脂肪筋 / メタボリックシンドローム / 糖尿病 / 骨格筋細胞内脂質 / 脂肪負荷感受性

Outline of Final Research Achievements

We defined individual differences in the susceptibility to ectopic fat accumulation and insulin sensitivity after fat loading as fat loading sensitivity, and verified their significance. A 6-day high-fat diet was performed on non-obese young healthy Japanese men aged 20 to 29 years. Skeletal muscle intracellular lipids and hepatic lipids increased by 47% and 200%, respectively. On the other hand, liver and muscle insulin sensitivity decreased by 8% and 4%, respectively. Fasting free fatty acids decreased by 43%, total ketone body levels decreased by 53%, and glucose oxidation during sleep increased. Thus, it was revealed that a high-fat diet results in ectopic fat accumulation and a slight decrease in insulin sensitivity, but rather increases glucose utilization, and there are large individual differences in these changes.

Academic Significance and Societal Importance of the Research Achievements

アジア人では非肥満者でも糖尿病やメタボリックシンドロームになりやすいが、その原因は不明の部分を多く残している。本研究では、脂肪負荷後の異所性脂肪蓄積やインスリン感受性の低下のし易さを脂肪負荷感受性と定義し、その個人差や意義などを検証した。今回の結果から、高脂肪食負荷後の変化には大きな個人差があることが明らかとなった。これらのことから、脂肪負荷感受性の個人差を念頭に置いた個別性のある代謝疾患の予防法の開発へ応用されることが期待される。

Research Products

• [Presentation] Higher relative abundance of bacteroidetes in gut microbiota is associated with decreased insulin clearance and insulin sensitivity after a short-term high-calorie, high-fat diet in healthy men. (2020)
  • Author(s): Kadowaki S, Tamura Y, Sugimoto D, Someya Y, Kaga H, Suzuki R, Kakehi S, Yamasaki N, Sato M, Kanazawa A, Kawamori R, Watada H.
  • Organizer: 80th American Diabetes Association, Chicago (USA), 2020.6.12-16. （ Poster, Virtual meeting）.
  • Int'l Joint Research
• [Presentation] Short-term overfeeding with dairy fat impairs insulin sensitivity in muscle and liver but increases adipose tissue insulin sensitivity and suppresses postprandial glucose rise in healthy non-obese men. (2020)
  • Author(s): Sugimoto D, Tamura Y, Kadowaki S, Someya Y, Kaga H, Suzuki R, Kakehi S, Yamasaki N, Sato M, Kanazawa A, Kawamori R, Watada H.
  • Organizer: 80th American Diabetes Association, Chicago (USA), 2020.6.12-16. （ Poster, Virtual meeting）.
  • Int'l Joint Research