Study on skeletal muscle proteolysis due to systemic metabolic dysfunction in broiler chickens exposed to heat stress

• Project/Area Number: 16H06205
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Animal production science
• Research Institution: Tohoku University
• Principal Investigator: Kikusato Motoi 東北大学, 農学研究科, 准教授 (90613042)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
• Keywords: 暑熱ストレス / 筋タンパク質分解 / 全身性炎症 / 酸化ストレス / 肉用鶏 / ブロイラー / 腸管 / 炎症 / 骨格筋 / タンパク質分解 / ニワトリ / 代謝 / アルギニン / アラニン / 腸管バリア機能 / 代謝産物 / サイトカイン / 胆汁酸 / ミトコンドリア / 活性酸素 / α-トコフェロール / ホルモン / グルココルチコイド / エンドトキシン / ミトコンドリア活性酸素

Outline of Final Research Achievements

This study was conducted to elucidate trans-organ metabolic network that induces muscle protein degradation in broiler chickens exposed to heat stress (HS). In the study, corticosterone (CORT), mitochondrial reactive oxygen species generation (mitROS), intestinal barrier function, inflammatory response, amino acid metabolism were evaluated. As a result, the study revealed that i) HS-induced muscle proteolysis could be attributed to mitROS rather than CORT, and that ii) LPS influx evoked by intestinal barrier dysfunction may stimulate 3-MH and CORT secretion, and iii) Arg generated by the muscle proteolysis might contribute to the amelioration of inflammation in HS-exposed broiler chickens. These findings suggest that HS-induced muscle proteolysis may occur in the systemic inflammation in broiler chickens.

Academic Significance and Societal Importance of the Research Achievements

これまでの暑熱ストレス研究は非常に多彩ではあったものの、酸化ストレスなどの単一の代謝変化の追究に固執した研究が多かった。本研究では、暑熱諸反応を臓器間代謝ネットワークの観点から体系的・統合的に紡ぎ合わせ、筋タンパク質分解と腸管機能、炎症反応の連関を実証した。これにより、家禽科学に対してストレス反応ネットワークの視点を提供し、また新たな暑熱ストレス制御法として腸管における抗炎症の生理的重要性を提示した。

Research Products

• [Int'l Joint Research] ルーベンカトリック大学(ベルギー)
• [Int'l Joint Research] ルーベンカトリック大学(ベルギー)
• [Journal Article] Heat Stress Directly Affects Intestinal Integrity in Broiler Chickens (2020)
  • Author(s): Nanto-Hara F, Kikusato M, Ohwada S, Toyomizu M
  • Journal Title: The Journal of Poultry Science Volume: 57 Issue: 4 Pages: 284-290
  • DOI: 10.2141/jpsa.0190004
  • NAID: 130007930410
  • ISSN: 1346-7395, 1349-0486
  • Peer Reviewed / Open Access
• [Journal Article] Differences in Breast Muscle Mitochondrial Respiratory Capacity, Reactive Oxygen Species Generation, and Complex Characteristics between 7-week-old Meat- and Laying-type Chickens (2020)
  • Author(s): Hakamata Y, Toyomizu M, Kikusato M
  • Journal Title: The Journal of Poultry Science Volume: 57 Issue: 4 Pages: 319-327
  • DOI: 10.2141/jpsa.0190133
  • NAID: 130007930423
  • ISSN: 1346-7395, 1349-0486
  • Peer Reviewed / Open Access
• [Journal Article] Heat Stress Causes Immune Abnormalities via Massive Damage to Effect Proliferation and Differentiation of Lymphocytes in Broiler Chickens (2020)
  • Author(s): Hirakawa Ryota、Nurjanah Siti、Furukawa Kyohei、Murai Atsushi、Kikusato Motoi、Nochi Tomonori、Toyomizu Masaaki
  • Journal Title: Frontiers in Veterinary Science Volume: 7 Pages: 46-46
  • DOI: 10.3389/fvets.2020.00046
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differential effects of heat stress on oxidative status of skeletal muscle with different muscle fibre compositions in broiler chicken (2019)
  • Author(s): Kikusato M, Toyomizu M
  • Journal Title: Journal of Animal and Feed Sciences Volume: 28 Issue: 1 Pages: 78-82
  • DOI: 10.22358/jafs/102830/2019
  • Peer Reviewed / Open Access
• [Journal Article] Nutritional regulation of mitochondrial ROS production of chickens exposed to acute and chronic heat stress (2019)
  • Author(s): Toyomizu M, Mujahid A, Hirakawa R, Furukawa K, Azad MAK, Taciak M, Kikusato M
  • Journal Title: Energy and protein metabolism and nutrition Volume: 138 Pages: 73-81
  • Peer Reviewed
• [Journal Article] Effects of low-dose oleuropein diet supplementation on the oxidative status of skeletal muscles and plasma hormonal concentration of growing broiler chickens (2019)
  • Author(s): Shimao R.、Muroi H.、Furukawa K.、Toyomizu M.、Kikusato M.
  • Journal Title: British Poultry Science Volume: 60 Issue: 6 Pages: 784-789
  • DOI: 10.1080/00071668.2019.1662886
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of Mitochondrial Content and Respiratory Capacities of Broiler Chicken Skeletal Muscles with Different Muscle Fiber Compositions (2018)
  • Author(s): 1.Hakamata, Y., Watanabe, K., Amo, T., Toyomizu, M. and Kikusato, M.
  • Journal Title: The Journal of Poultry Science Volume: 55 Issue: 3 Pages: 210-216
  • DOI: 10.2141/jpsa.0170141
  • NAID: 130007419002
  • ISSN: 1346-7395, 1349-0486
  • Peer Reviewed / Open Access
• [Journal Article] Roles of mitochondrial oxidative phosphorylation and reactive oxygen species generation in the metabolic modification of avian skeletal muscle (2016)
  • Author(s): Motoi Kikusato, Kyohei Furukawa, Tomomi, Kamizono, Yuki Hakamata and Masaaki Toyomizu
  • Journal Title: Proceedings of Japan Society of Animal Nutrition and Metabolism Volume: 60 Pages: 57-68
  • NAID: 40020901552
  • Peer Reviewed
• [Presentation] ブロイラーの環境ストレスにおよぼすBacillus amyloliquefaciens strain TOA5001の給与効果 (2020)
  • Author(s): 喜久里基・福井和夫・豊水正昭
  • Organizer: 日本家禽学会春季大会（2020年3月28日）
• [Presentation] Evaluation of isoquinoline alkaloidsas alternative to antimicrobial growth promotors in broiler chickens (2019)
  • Author(s): Kikusato M, Xue G, Pastor A, Toyomizu M
  • Organizer: 22th Europena Symposium on Poultry Nutrition
  • Int'l Joint Research
• [Presentation] Effects of feeding isoquinoline alkaloids on the grow performance of broiler chickens under heat-stressed conditions (2019)
  • Author(s): Kikusato M, Xue G, Pastor A, Toyomizu M
  • Organizer: 22th Europena Symposium on Poultry Nutrition
  • Int'l Joint Research
• [Presentation] 暑熱感作鶏の骨格筋タンパク質分解に対するグルタミン・グルタミン酸同時給与の抑制効果 (2019)
  • Author(s): 古川恭平・喜久里基・Wu Guoyao・豊水正昭
  • Organizer: 日本家禽学会2019年春季大会
• [Presentation] 鶏における暑熱感作時の骨格筋タンパク質分解亢進の分子メカニズムの解明 (2018)
  • Author(s): 古川恭平・喜久里基・豊水正昭
  • Organizer: 日本家禽学会2018年秋季大会
• [Presentation] Differences in mitochondrial fatty acid utilization and respiratory complex characteristics between meat-type and laying-type chickens (2018)
  • Author(s): Hakamata Y, Amo T, Toyomizu M, Kikusato, M
  • Organizer: 11th Asia Pacific Poultry Conference
  • Int'l Joint Research
• [Presentation] 生理的濃度のコルチコステロンはニワトリ高温培養筋細胞のタンパク質分解を増強しない (2017)
  • Author(s): 古川恭平・喜久里基・豊水正昭
  • Organizer: 日本畜産学会第122回大会
  • Place of Presentation: 神戸大学鶴甲第1キャンパス（神戸市灘区、兵庫県）
  • Year and Date: 2017-03-28
• [Presentation] Oleuropein suppresses oxidative damage in avian skeletal muscle, possibly via SIRT1 up-regulation (2017)
  • Author(s): Kikusato M, Shimao R, Muroi H, Toyomizu, M
  • Organizer: 21st European Symposium on Poultry Nutrition
  • Int'l Joint Research
• [Presentation] Roles of corticosterone and superoxide in the ubiquitin proteasome system in heat-stressed chickens (2016)
  • Author(s): Furukawa, K., Kikusato, M. and Toyomizu, M.
  • Organizer: 5th EAAP International Symposium on Energy and Protein Metabolism and Nutrition
  • Place of Presentation: Krakow, Poland
  • Year and Date: 2016-09-12
  • Int'l Joint Research
• [Presentation] Time-course of changes in muscle antioxidant peptide concentrations in heat-stressed broiler chickens (2016)
  • Author(s): Furukawa, K., Waki, N, Kikusato, M., Ashinara, A., Ishida, A., Nakashima, K. and Toyomizu, M.
  • Organizer: 17th Animal Science Congress of Asian Australasian Animal Production
  • Place of Presentation: 九州産業大学、福岡市東区、福岡県
  • Year and Date: 2016-08-22
  • Int'l Joint Research