Functional dietary lipids and gut microbiota on metabolic disorders

• Project/Area Number: 18K17920
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Miyamoto Junki 東京農工大学, (連合)農学研究科(研究院), 准教授 (20805668)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 腸内細菌 / 腸内細菌代謝物 / 食用油 / 肥満 / エネルギー代謝 / 内分泌 / GLP-1 / gut microbial metabolite / gut microbiota / FFARs / obesity / dietary lipid / GPCRs / free fatty acid receptor / 脂肪酸受容体

Outline of Final Research Achievements

The present study provided that gut microbial metabolites derived from dietary lipids prevent high fat diet-induced obesity. Gut microbial metabolites contribute to promoting the secretion of GLP-1 via GPR40/GPR120 in enteroendocrine cells and regulate glucose homeostasis. These findings suggest that gut microbial metabolites derived from dietary lipids could contribute to the development of novel therapeutic strategies for metabolic disorders.

Academic Significance and Societal Importance of the Research Achievements

近年の腸内細菌研究の発展に伴い、様々な病態と密接に関与することが科学的根拠に基づいて明らかにされ始めている。本研究における食用油－腸内環境－生体側の受容体を介した生体エネルギー代謝調節の解明は、新たな代謝性疾患における治療標的となる可能性が示唆される。今後、機能性食用油の摂取、プロバイオティクス様の腸内細菌代謝産生菌の投与、さらには、腸内細菌代謝物の直接的な摂取による代謝性疾患に対する新たな治療法の開発が期待される。

Research Products

• [Journal Article] Gut microbial short-chain fatty acids-mediated olfactory receptor 78 stimulation promotes anorexigenic gut hormone peptide YY secretion in mice. (2021)
  • Author(s): Nishida A, Miyamoto J, Shimizu H, Kimura I.
  • Journal Title: Biochem Biophys Res Commun. Volume: 557 Pages: 48-54
  • DOI: 10.1016/j.bbrc.2021.03.167
  • Peer Reviewed / Open Access
• [Journal Article] Lecithin Inclusion by α-Cyclodextrin Activates SREBP2 Signaling in the Gut and Ameliorates Postprandial Hyperglycemia (2021)
  • Author(s): Lee Eunyoung、Zhang Xilin、Noda Tomoe、Miyamoto Junki、Kimura Ikuo、Tanaka Tomoaki、Sakurai Kenichi、Hatano Ryo、Miki Takashi
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 19 Pages: 10796-10796
  • DOI: 10.3390/ijms221910796
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice (2020)
  • Author(s): Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T, Onuki M, Aoki R, Isobe Y, Kashihara D, Inoue D, Inaba A, Takamura Y, Taira S, Kumaki S, Watanabe M, Ito M, Nakagawa F, Irie J, Kakuta H, Shinohara M, Iwatsuki K, Tsujimoto G, Ohno H, Arita M, Itoh H, Hase K.
  • Journal Title: Science Volume: 367 Issue: 6481 Pages: 8429-8429
  • DOI: 10.1126/science.aaw8429
  • Peer Reviewed / Open Access
• [Journal Article] Contribution of uremic dysbiosis to insulin resistance and sarcopenia. (2020)
  • Author(s): Uchiyama K, Wakino S, Irie J, Miyamoto J, Matsui A, Tajima T, Itoh T, Oshima Y, Yoshifuji A, Kimura I, Itoh H.
  • Journal Title: Nephrol Dial Transplant. Volume: 35 Issue: 9 Pages: 1501-1517
  • DOI: 10.1093/ndt/gfaa076
  • Peer Reviewed
• [Journal Article] 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid Produced from 4-Hydroxy-3-methoxycinnamic Acid by Gut Microbiota Improves Host Metabolic Condition in Diet-Induced Obese Mice. (2019)
  • Author(s): Ohue-Kitano R, Taira S, Watanabe K, Masujima Y, Kuboshima T, Miyamoto J, Nishitani Y, Kawakami H, Kuwahara H, Kimura I.
  • Journal Title: Nutrients. Volume: 11 Issue: 5 Pages: 1036-1036
  • DOI: 10.3390/nu11051036
  • Peer Reviewed / Open Access
• [Journal Article] Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids (2019)
  • Author(s): Miyamoto J, Igarashi M, Watanabe K, Karaki SI, Mukouyama H, Kishino S, Li X, Ichimura A, Irie J, Sugimoto Y, Mizutani T, Sugawara T, Miki T, Ogawa J, Drucker DJ, Arita M, Itoh H, Kimura I
  • Journal Title: Nat Commun Volume: 10 Issue: 1 Pages: 1-15
  • DOI: 10.1038/s41467-019-11978-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diet-Induced Obese Mice and Leptin-Deficient Lepob/ob Mice Exhibit Increased Circulating GIP Levels Produced by Different Mechanisms (2019)
  • Author(s): Lee Eunyoung、Miedzybrodzka Emily L.、Zhang Xilin、Hatano Ryo、Miyamoto Junki、Kimura Ikuo、Fujimoto Kosuke、Uematsu Satoshi、Rodriguez-Cuenca Sergio、Vidal-Puig Antonio、Gribble Fiona M.、Reimann Frank、Miki Takashi
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 18 Pages: 4448-4448
  • DOI: 10.3390/ijms20184448
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions (2019)
  • Author(s): Miyamoto J, Ohue-Kitano R, Mukouyama H, Nishida A, Watanabe K, Igarashi M, Irie J, Tsujimoto G, Satoh-Asahara N, Itoh H, Kimura I
  • Journal Title: Proc Natl Acad Sci USA Volume: 116 Issue: 47 Pages: 23813-23821
  • DOI: 10.1073/pnas.1912573116
  • Peer Reviewed / Open Access
• [Journal Article] Gut carbohydrate inhibits GIP secretion via a microbiota/SCFA/FFAR3 pathway (2018)
  • Author(s): Lee Eun-Young、Zhang Xilin、Miyamoto Junki、Kimura Ikuo、Taknaka Tomoaki、Furusawa Kenichi、Jomori Takahito、Fujimoto Kosuke、Uematsu Satoshi、Miki Takashi
  • Journal Title: Journal of Endocrinology Volume: 239 Issue: 3 Pages: 267-276
  • DOI: 10.1530/joe-18-0241
  • Peer Reviewed / Open Access
• [Journal Article] Dietary soybean protein ameliorates high-fat diet-induced obesity by modifying the gut microbiota-dependent biotransformation of bile acids. (2018)
  • Author(s): Watanabe K, Igarashi M, Li X, Nakatani A, Miyamoto J, Inaba Y, Sutou A, Saito T, Sato T, Tachibana N, Inoue H, Kimura I.
  • Journal Title: PLoS One. Volume: 13 Issue: 8 Pages: e0202083-e0202083
  • DOI: 10.1371/journal.pone.0202083
  • Peer Reviewed / Open Access
• [Journal Article] Dietary mung bean protein reduces high-fat diet-induced weight gain by modulating host bile acid metabolism in a gut microbiota-dependent manner. (2018)
  • Author(s): Nakatani A, Li X, Miyamoto J, Igarashi J, Watanabe H, Sutou A, Watanabe K, Motoyama T, Tachibana N, Kohno M, Inoue H, Kimura I.
  • Journal Title: Biochem Biophys Res Commun. Volume: 501 Issue: 4 Pages: 955-961
  • DOI: 10.1016/j.bbrc.2018.05.090
  • Peer Reviewed / Open Access
• [Journal Article] Barley β-glucan improves metabolic condition via short-chain fatty acids produced by gut microbial fermentation in high fat diet fed mice. (2018)
  • Author(s): Miyamoto J, Watanabe K, Taira S, Kasubuchi M, Li X, Irie J, Itoh H, Kimura I.
  • Journal Title: PLoS One. Volume: 13 Issue: 4 Pages: e0196579-e0196579
  • DOI: 10.1371/journal.pone.0196579
  • Peer Reviewed / Open Access
• [Presentation] 新規短鎖脂肪酸受容体 Olfr78 を介した代謝調節機構の解明 (2021)
  • Author(s): 西田朱里、宮本潤基、清水秀憲、木村郁夫
  • Organizer: 内分泌代謝学サマーセミナー
• [Presentation] 母胎連関における食由来代謝物と生体エネルギー代謝調節 (2021)
  • Author(s): 安藤有菜、宮本潤基、木村郁夫
  • Organizer: 内分泌代謝学サマーセミナー
• [Presentation] 食由来腸内細菌代謝物の脂肪酸受容体を介したエネルギー代謝調節 (2021)
  • Author(s): 宮本潤基、入江潤一郎、伊藤裕、木村郁夫
  • Organizer: 第42回日本肥満学会
• [Presentation] Metabolic regulation via ketone body receptors under ketogenic conditions (2021)
  • Author(s): Nishida Akari, Junki Miyamoto, Ryuji Ohue-Kitano, Hironori Katoh, Ikuo Kimura
  • Organizer: Experimental Biology 2021
  • Int'l Joint Research
• [Presentation] 食・栄養シグナルの分子レベルでの解明；栄養シグナルとしての脂肪酸の利用 (2021)
  • Author(s): 宮本潤基
  • Organizer: Visionary農芸化学100 symposium（食品機能学領域）
  • Invited
• [Presentation] 脂肪酸受容体とエネルギー代謝調節 (2021)
  • Author(s): 宮本潤基、木村郁夫
  • Organizer: 第37回DDS学会
  • Invited
• [Presentation] 食由来腸内細菌代謝物と肥満 (2021)
  • Author(s): 宮本潤基
  • Organizer: 第39回日本内分泌学会 内分泌代謝学サマーセミナー
  • Invited
• [Presentation] 創薬応用に向けた栄養認識受容体と肥満 (2021)
  • Author(s): 宮本潤基、木村郁夫
  • Organizer: 日本薬理学会次世代の会
  • Invited
• [Presentation] 食事脂質由来腸内細菌代謝産物と宿主エネルギー代謝制御 (2020)
  • Author(s): 向山広美、宮本潤基、五十嵐美樹、木村郁夫
  • Organizer: 日本農芸化学会2020年度大会
• [Presentation] ケトジェニック環境下におけるGPR109Aの機能解析 (2020)
  • Author(s): 西田朱里、大植隆司、宮本潤基、木村郁夫
  • Organizer: 日本栄養食糧学会第74回大会
• [Presentation] GPCRs for ketone bodies and energy homeostasis (2020)
  • Author(s): 宮本潤基
  • Organizer: 第93回日本薬理学会年会
  • Invited
• [Presentation] 食由来栄養シグナルと宿主エネルギー代謝調節 (2020)
  • Author(s): 宮本潤基
  • Organizer: 第51回HiHA Webinar
  • Invited
• [Presentation] 食由来腸内細菌代謝物とエネルギー制御 (2020)
  • Author(s): 宮本潤基、木村郁夫
  • Organizer: 第9回Academy of Aging and CArdiovascular-Diabetes Research研究会
  • Invited
• [Presentation] 食由来腸内細菌代謝物と肥満 (2020)
  • Author(s): 宮本潤基
  • Organizer: 第41回日本肥満学会・第38回日本肥満症治療学会
  • Invited
• [Presentation] Host energy regulation by gut microbial metabolites derived from ω6 polyunsaturated fatty acids. (2019)
  • Author(s): Miyamoto J, Igarashi M, Sugimoto Y, Arita M, Kimura I
  • Organizer: 60th International Conference on the Bioscience of Lipids (ICBL2019)
  • Int'l Joint Research
• [Presentation] Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids. (2019)
  • Author(s): Miyamoto J, Mukouyama H, Kimura I
  • Organizer: Winter conference 2019: Diet and Digestive disease
  • Int'l Joint Research
• [Presentation] 腸内環境と栄養シグナルによる宿主エネルギー代謝制御機構の解明 (2019)
  • Author(s): 宮本潤基、北野（大植）隆司、五十嵐美樹、入江潤一郎、伊藤裕、木村郁夫
  • Organizer: 第92回日本内分泌学会学術総会
  • Int'l Joint Research
• [Presentation] ケトジェニック環境下におけるGPR43の機能解析 (2019)
  • Author(s): 宮本潤基、北野（大植）隆司、五十嵐美樹、入江潤一郎、伊藤裕、木村郁夫
  • Organizer: 第19回日本抗加齢医学会総会
  • Int'l Joint Research
• [Presentation] 食由来栄養シグナルと腸内環境を介した宿主エネルギー代謝制御 (2019)
  • Author(s): 宮本潤基、木村郁夫
  • Organizer: 生理学研究所研究会
  • Int'l Joint Research
• [Presentation] 食事脂質由来腸内細菌代謝物と宿主生体恒常性維持 (2018)
  • Author(s): 宮本潤基、木村郁夫
  • Organizer: 第9回機能油脂懇話会
  • Invited
• [Presentation] Gut microbiota and free fatty acid receptors mediated host energy regulation (2018)
  • Author(s): Miyamoto Junki, Kimura Ikuo
  • Organizer: AOCS Annual Meeting & Expo
  • Int'l Joint Research / Invited
• [Presentation] 腸内細菌代謝物と腸管バリア (2018)
  • Author(s): 宮本潤基、鈴木卓弥、木村郁夫、田辺創一
  • Organizer: 第22回日本心血管内分泌代謝学会学術総会
• [Presentation] 脂肪酸受容体を介した腸内細菌代謝物の包括的なエネルギー代謝制御機構の解明 (2018)
  • Author(s): 宮本潤基、唐木晋一郎、岸野重信、入江潤一郎、菅原達也、杉本幸彦、有田誠、小川順、伊藤裕、木村郁夫
  • Organizer: 第91回日本内分泌学会学術集会
• [Book] ケトン体（アセト酢酸）の受容体を介した脂質代謝 (2021)
  • Author(s): 西田朱里、宮本潤基、木村郁夫
  • Total Pages: 3
  • Publisher: 化学と生物
• [Book] 妊娠中の食物繊維摂取と胎児の代謝 (2021)
  • Author(s): 渡辺啓太、西田朱里、宮本潤基、木村郁夫
  • Total Pages: 9
  • Publisher: 糖尿病学2021
• [Book] 腸内環境と肥満 (2021)
  • Author(s): 宮本潤基、木村郁夫
  • Total Pages: 4
  • Publisher: Medical Practice.
• [Book] 食と腸内細菌による宿主の代謝制御 (2021)
  • Author(s): 宮本潤基、渡辺啓太、木村郁夫
  • Total Pages: 186
  • Publisher: 生化学
• [Book] ケトン体生成を促す食事療法による体脂肪減少メカニズム (2020)
  • Author(s): 渡辺啓太、向山広美、宮本潤基、木村郁夫
  • Total Pages: 287
  • Publisher: バイオサイエンスとインダストリー（B&I）
• [Book] 腸内細菌叢と肥満（脂質） (2020)
  • Author(s): 向山広美、宮本潤基、木村郁夫
  • Total Pages: 624
  • Publisher: ヒトマイクロバイオーム最前線
• [Book] 食由来栄養シグナルと腸内環境を介した宿主エネルギー代謝制御 (2020)
  • Author(s): 渡辺啓太、向山広美、宮本潤基、木村郁夫
  • Total Pages: 78
  • Publisher: 糖尿病・内分泌代謝科
• [Book] 妊娠中の母体の代謝がこどもに与える影響 (2020)
  • Author(s): 宮本潤基、渡辺啓太、木村郁夫、長谷耕二
  • Total Pages: 123
  • Publisher: 臨床免疫・アレルギー科
• [Book] 腸内細菌とDOHaD学説 (2020)
  • Author(s): 宮本潤基、渡辺啓太、木村郁夫
  • Total Pages: 116
  • Publisher: Pharma Medica
• [Book] 胎児期・乳児期の腸内細菌叢の長期的影響 (2020)
  • Author(s): 渡辺啓太、宮本潤基、長谷耕二、木村郁夫
  • Total Pages: 70
  • Publisher: 医学のあゆみ 特集号
• [Book] 低炭水化物食における分子栄養メカニズム (2020)
  • Author(s): 西田朱里、宮本潤基、大植隆司、木村郁夫
  • Total Pages: 89
  • Publisher: Pharma Medica
• [Book] 宿主エネルギー代謝制御における腸内細菌と遊離脂肪酸の役割 (2019)
  • Author(s): 向山広美, 宮本潤基
  • Total Pages: 6
  • Publisher: オレオサイエンス
• [Book] 短鎖脂肪酸による疾患制御 (2019)
  • Author(s): 宮本潤基, 木村郁夫
  • Total Pages: 5
  • Publisher: 医学のあゆみ 特集号
• [Book] 腸内細菌叢を標的にした医薬品と保健機能食品の開発 (2018)
  • Author(s): 宮本潤基、木村郁夫
  • Total Pages: 8
  • Publisher: 技術情報協会
• [Book] 脂肪酸代謝と腸内環境 (2018)
  • Author(s): 宮本潤基、中谷明穂、木村郁夫
  • Total Pages: 6
  • Publisher: アンチ・エイジング医学
• [Book] 肥満と腸内細菌叢 (2018)
  • Author(s): 渡辺啓太、宮本潤基、木村郁夫
  • Total Pages: 4
  • Publisher: Modern Physician.
• [Remarks] 妊娠中の食物繊維摂取は胎児の代謝機能の発達を促し、出生後、子の肥満になりにくい体質をつくる
  • URL: https://www.tuat.ac.jp/outline/disclosure/pressrelease/2019/20200226_01.html
• [Remarks] 腸内細菌は食用油に含まれる多価不飽和脂肪酸を代謝することにより宿主の肥満を防ぐことを解明
  • URL: https://www.tuat.ac.jp/outline/disclosure/pressrelease/2019/20190905_01.html
• [Remarks] 低炭水化物食や断続的断食による減量メカニズムの解明―ケトン体の新たな受容体を発見―
  • URL: https://www.tuat.ac.jp/outline/disclosure/pressrelease/2019/20191101_01.html