Regulation of gut nutrient sensing mechanisms in response to dietary intervention

• Project/Area Number: 16K07725
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Hokkaido University
• Principal Investigator: Hira Tohru 北海道大学, 農学研究院, 講師 (10396301)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 消化管ホルモン / 食事誘導性肥満 / 消化管内分泌系 / GLP-1 / 栄養素感受性 / 肥満誘導食

Outline of Final Research Achievements

We have previously demonstrated that continuous feeding of a high fat and high sucrose diet enhanced nutrient-induced GLP-1 secretion in rats. In this research project, we revealed that the high fat diet, rather than the high sucrose diet, has potent impact on enhancement of nutrient-induced GLP-1 secretion. In addition, the adaptive changes in nutrient-induced GLP-1 secretion was rapidly occurred in young rats than adult rats. Furthermore, by conducting continuous administration of GLP-1 receptor antagonist, we found that the increased GLP-1 response has a role to prevent from glucose intolerance during the development of diet-induced obesity.

Academic Significance and Societal Importance of the Research Achievements

本研究により、肥満誘導食のどのような食事成分が栄養素感受性を亢進(あるいは減弱)させるか、その感受性亢進（食後GLP-1分泌応答の増大）の生理的意義が明らかにされた。これらの研究成果は、消化管内分系に関する新たな学術的基盤の構築に大きく貢献すると期待される。
また、栄養素感受性の亢進（食後GLP-1分泌応答の増大）が、耐糖能異常に対して防御的にはたらくことを明らかにしたことは、これを効果的に活性化する食品成分や薬剤の開発を通じて、耐糖能異常の効果的な予防策が提案できると考えられる。

Research Products

• [Journal Article] Continuous feeding of a combined high-fat and high-sucrose diet, rather than an individual high-fat or high-sucrose diet, rapidly enhances the glucagon-like peptide-1 secretory response to meal ingestion in diet-induced obese rats (2019)
  • Author(s): Pinyo Jukkrapong、Hira Tohru、Hara Hiroshi
  • Journal Title: Nutrition Volume: 62 Pages: 122-130
  • DOI: 10.1016/j.nut.2019.01.004
  • Peer Reviewed
• [Journal Article] Impact of difructose anhydride III, raffinose, and fructooligosaccharides on energy intake, gut hormones, and cecal fermentation in rats fed a high-fat and high-sucrose diet. (2017)
  • Author(s): Hira T, Yanagihara K, Koga T, Takahashi K, Nagura T, Uchino H, Hara H.
  • Journal Title: Biosci Biotechnol Biochem. Volume: 81 Issue: 11 Pages: 2186-2194
  • DOI: 10.1080/09168451.2017.1373591
  • Peer Reviewed
• [Presentation] Postprandial GLP-1 response in Wistar and Goto-Kakizaki rats during diet-induced obesity (2018)
  • Author(s): Jukkrapong PINYO, Tohru HIRA, Hiroshi HARA
  • Organizer: Asia-Pacific Diabetes and Obesity Study Group, Joint with the 39th Annual Meeting of Japan Society for the Study of Obesity
  • Int'l Joint Research
• [Presentation] 難消化性糖質の消化管内分泌系への作用 (2018)
  • Author(s): 比良 徹、原 博
  • Organizer: 第72回日本栄養・食糧学会大会シンポジウム（共催：Hindgut Club Japan）
  • Invited
• [Presentation] 食品成分による消化管内分泌系のコントロール 主にGLP-1に関して (2018)
  • Author(s): 比良 徹
  • Organizer: 第98回北海道医学大会生理系分科会・日本生理学会北海道地方会
  • Invited
• [Presentation] Impact of chronic high fat and/or high sucrose feeding on meal-induced GLP-1 secretion (2017)
  • Author(s): Jukkrapong PINYO, Tohru HIRA, Hiroshi HARA
  • Organizer: 日本農芸化学会 2017年度大会
  • Place of Presentation: 京都女子大学（京都府京都市）
  • Year and Date: 2017-03-17
• [Presentation] 肥満誘導食摂取ラットにおける食事刺激に対するGLP-1分泌応答の解析 (2017)
  • Author(s): 柳原 くるみ、比良 徹、原 博
  • Organizer: 日本栄養・食糧学会第71回大会
• [Presentation] The role of endogenous GLP-1 against the development of glucose intolerance in rats fed a high fat and high sucrose diet (2017)
  • Author(s): Jukkrapong Pinyo, Tohru Hira, Hiroshi Hara
  • Organizer: 平成29年度日本農芸化学会北海道支部第１回講演会
• [Presentation] GLP-1を増やす食品成分、食事条件 (2017)
  • Author(s): 比良 徹
  • Organizer: 平成２９年度 公益社団法人日本農芸化学会 北海道支部第２回講演会および公益社団法人日本栄養・食糧学会 第47回北海道支部大会合同大会
• [Presentation] "肥満誘導食摂取ラットにおけるカナグリフロジン経口投与に対するGLP-1分泌応答 " (2016)
  • Author(s): 比良 徹、古賀 俊希、石井 伸一、佐々木 一代、原 博
  • Organizer: 第37回日本肥満学会
  • Place of Presentation: 東京ファッションタウン（東京都）
  • Year and Date: 2016-10-07
• [Presentation] Effect of high fat and/or high sucrose diet on meal-induced GLP-1 secretion during the progression of diet induced obesity in rats (2016)
  • Author(s): Jukkrapong Pinyo, Tohru Hira, Hiroshi Hara
  • Organizer: 平成28年度日本農芸化学会北海道支部第２回講演会
  • Place of Presentation: 北海道大学農学部（北海道札幌市）