Basic study on the creation of novel therapeutic approach by the regulation of the metabolism of branched chain amino acids

• Project/Area Number: 24688015
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Food science
• Research Institution: Kyoto University
• Principal Investigator: Goto Tsuyoshi 京都大学, (連合)農学研究科(研究院), 准教授 (10550311)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2012: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
• Keywords: 肥満 / 脂肪組織 / 分岐鎖アミノ酸 / アミノ酸 / 脂肪細胞 / PPAR / 食品

Outline of Final Research Achievements

In this study, we investigated the relationship between obesity and amino acids metabolism, including branched-chain amino acids (BCAAs). We showed following findings. 1. Mice lacking Bcat2, a gene related to BCAAs metabolism, in adipose tissue didn't show any changes in non-fasting plasma BCAAs levels and adiposity, suggesting that the increment of plasma BCAAs levels under obesity condition didn't depend only on the down-regulation of BCAAs metabolism in obese adipose tissues. 2. Agonists of PPARγ, a master regulator of adipocyte differentiation, were involved in the regulation of whole body amino acid metabolism via the activation of PPARγ in adipocytes. 3. Activation of PPARα in adipose tissues lowered plasma BCAAs levels under high-fat diet feeding condition.

Research Products

• [Int'l Joint Research] University of Ulsan(韓国)
• [Journal Article] Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 expression in mice. (2016)
  • Author(s): Sakamoto T, Nitta T, Maruno K, Yeh YS, Kuwata H, Tomita K, Goto T, Takahashi N, Kawada T.
  • Journal Title: Am. J. Physiol. Endocrinol. Metab. Volume: - Issue: 8 Pages: E676-E687
  • DOI: 10.1152/ajpendo.00028.2015
  • Peer Reviewed
• [Journal Article] Proinflammatory cytokine interleukin-1β suppresses cold-induced thermogenesis in adipocytes. (2016)
  • Author(s): Goto T, Naknukool S, Yoshitake R, Hanafusa Y, Tokiwa S, Li Y, Sakamoto T, Nitta T, Kim M, Takahashi N, Yu R, Daiyasu H, Seno S, Matsuda H, Kawada T.
  • Journal Title: Cytokine. Volume: 77 Pages: 107-114
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fish oil intake induces UCP1 upregulation in brown and white adipose tissue via the sympathetic nervous system. (2015)
  • Author(s): Minji Kim, Tsuyoshi Goto, Rina Yu, Kunitoshi Uchida, Makoto Tominaga, Yuriko Oi-Kano, Nobuyuki Takahashi, and Teruo Kawada
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 18013-18013
  • DOI: 10.1038/srep18013
  • NAID: 120005690138
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α. (2015)
  • Author(s): Takahashi H, Goto T, Yamazaki Y, Kamakayi K, Hirata M, Suzuki H, Shibata D, Takahashi N, Kawada T.
  • Journal Title: J Lipid Res. Volume: 56 Issue: 2 Pages: 254-265
  • DOI: 10.1194/jlr.m052464
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 13-Oxo-9(Z),11(E),15(Z)-octadecatrienoic acid activates peroxisome proliferator-activated receptor γ in adipocytes. (2015)
  • Author(s): Takahashi H, Hara H, Goto T, Kamakari K, Wataru N, Mohri S, Takahashi N, Suzuki H, Shibata D, Kawada T.
  • Journal Title: Lipids Volume: 50 Issue: 1 Pages: 3-12
  • DOI: 10.1007/s11745-014-3972-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARgamma and stimulates adipogenesis. (2015)
  • Author(s): Goto T, Kim YI, Furuzono T, Takahashi N, Yamakuni K, Yang HE, Li Y, Ohue R, Nomura W, Sugawara T, Yu R, Kitamura N, Park SB, Kishino S, Ogawa J, Kawada T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 459 Issue: 4 Pages: 597-603
  • DOI: 10.1016/j.bbrc.2015.02.154
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Long-chain free fatty acid profiling analysis by liquid chromatography-mass spectrometry in mouse treated with peroxisome proliferator-activated receptor α agonist. (2013)
  • Author(s): Takahashi H, Suzuki H, Suda K, Yamazaki Y, Takino A, Kim YI, Goto T, Iijima Y, Aoki K, Shibata D, Takahashi N, Kawada T.
  • Journal Title: Biosci Biotechnol Biochem. Volume: 77 Pages: 2288-2293
  • NAID: 130003381942
  • Peer Reviewed
• [Journal Article] Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors. (2013)
  • Author(s): Goto T, Kim YI, Takahashi N, Kawada T.
  • Journal Title: Mol Nutr Food Res. Volume: 57 Issue: 1 Pages: 20-33
  • DOI: 10.1002/mnfr.201200522
  • Peer Reviewed
• [Journal Article] Soluble soy protein peptic hydrolysate stimulates adipocyte differentiation in 3T3-L1 cells. (2013)
  • Author(s): Tsuyoshi Goto, et al.
  • Journal Title: Mol Nutr Food Res. Volume: (印刷中) Issue: 8 Pages: 1435-45
  • DOI: 10.1002/mnfr.201200573
  • Peer Reviewed
• [Presentation] 核内受容体PPARα活性化因子による代謝異常改善機構の解析 (2015)
  • Author(s): 後藤剛、高橋春弥、高橋信之、河田照雄
  • Organizer: 第36回 日本肥満学会
  • Place of Presentation: 名古屋国際会議場 （愛知、名古屋）
  • Year and Date: 2015-10-02
  • Invited
• [Presentation] Xanthoangerol and 4-hydroxyderrcin supress obesity-induced inflammatory responses (2015)
  • Author(s): Li Y, Goto T, Ikutani R, Lin S, Takahashi N, Takahashi H, Jheng HF, Murakami S, Yu R, Kawada T.
  • Organizer: The 8th Asis-Oceania Conference on Obesity
  • Place of Presentation: Nagoya Congress Center (Aichi, Nagoya)
  • Year and Date: 2015-10-02
  • Int'l Joint Research
• [Presentation] The effect of IL-1 beta on UCP1 expression in adipocytes (2015)
  • Author(s): Hanafusa Y, Yoshitake R, Naknukool S, Sakamoto T, Daiyasu H, Seno S, Matsuda H, Goto T, Takahashi N, Kawada T.
  • Organizer: 12th Asian Congress of Nutrition
  • Place of Presentation: Pacifico Yokohama (Kanagawa, Yokohama)
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] 外因性因子による褐色脂肪細胞 機能亢進機構の解析 (2015)
  • Author(s): 後藤 剛、高橋 信之、河田 照雄
  • Organizer: 日本農芸化学会２０１５大会
  • Place of Presentation: 岡山大学 津島キャンパス
  • Year and Date: 2015-03-29
• [Presentation] 肥満に伴い脂肪組織に浸潤したマクロファージがベージュ脂肪細胞発現を抑制する (2015)
  • Author(s): 新田 貴大、坂本 智弥、丸野 晃嗣、後藤 剛、高橋 信之、河田 照雄
  • Organizer: 日本農芸化学会２０１５大会
  • Place of Presentation: 岡山大学 津島キャンパス
  • Year and Date: 2015-03-27
• [Presentation] ＩＬ－１βが白色脂肪細胞におけるUCP1発現に及ぼす影響 (2014)
  • Author(s): 吉竹 里依子、Naknukool Supaporn、花房 祐希、坂本 智弥、後藤 剛、高橋 信之、大安 裕美、瀬尾 茂人、松田 秀雄、河田 照雄
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎市 シーガイアコンベンションセンター
  • Year and Date: 2014-10-25
• [Presentation] 炎症誘発性一酸化窒素が白色脂肪細胞組織におけるPPARα発現に及ぼす作用 (2014)
  • Author(s): 青木 ゆめこ、後藤 剛、高橋 信之、河田 照雄
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎市 シーガイアコンベンションセンター
  • Year and Date: 2014-10-25
• [Presentation] PPARαアゴニストの薬理作用におけるFGF21の役割 (2014)
  • Author(s): 平田 茉莉子、後藤 剛、高橋 信之、伊藤 信行、河田 照雄
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎市 シーガイアコンベンションセンター
  • Year and Date: 2014-10-24
• [Presentation] PPARsアゴニストによる白色脂肪組織の褐色化に関する研究 (2014)
  • Author(s): 平田 茉莉子、後藤 剛、新田 貴大、高橋 信之、河田 照雄
  • Organizer: 第68回日本栄養・食糧学会
  • Place of Presentation: 江別市 酪農学園大学
  • Year and Date: 2014-06-01
• [Presentation] 褐色脂肪細胞機能と食品由来因子 細胞・モデル動物を用いた探索・評価法 (2014)
  • Author(s): 後藤 剛
  • Organizer: 第68回日本栄養・食糧学会
  • Place of Presentation: 江別市 酪農学園大学
  • Year and Date: 2014-05-31
• [Presentation] Farnesol Improves Obesityinduced Metabolic Disorders Via PPARαdependent And independent Pathways. (2014)
  • Author(s): 後藤 剛
  • Organizer: 12tha International Congress on Obesity
  • Place of Presentation: マレーシア クアラルンプール
• [Remarks] 京都大学 大学院農学研究科 食品生物科学専攻 食品分子機能学分野
  • URL: http://www.foodfunc.kais.kyoto-u.ac.jp/index.html
• [Remarks] 食品分子機能学分野ＨＰ
  • URL: http://www.foodfunc.kais.kyoto-u.ac.jp/
• [Remarks] 食品分子機能学分野ＨＰ
  • URL: http://www.foodfunc.kais.kyoto-u.ac.jp/results.html
• [Remarks]
  • URL: http://www.foodfunc.kais.kyoto-u.ac.jp/index.html