血管拡張因子：ａｄｒｏｐｉｎの運動による動脈硬化改善の貢献度とその調節機序の解明

• Project/Area Number: 18J01024
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: Applied health science (A)
• Research Institution: University of Tsukuba
• Principal Investigator: 藤江 隼平 筑波大学, 体育系, 特別研究員(PD)
• Project Period (FY): 2018-04-25 – 2021-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: adropin / 一酸化窒素 / 有酸素性トレーニング / 動脈硬化 / 高齢者 / 中高齢者

Outline of Annual Research Achievements

現在までに中高齢者の有酸素性トレーニングにより血中adropin濃度が増大し、その増大は動脈硬化度の低下や血管拡張物質である一酸化窒素(NO)の血中濃度の増大と関連があることを明らかにした。しかしながら、有酸素性トレーニングによる血中adropin濃度の増大はどの組織からの分泌増大を反映しているのかは明らかでない。そこで本研究課題では、有酸素性トレーニングによる血中adropin濃度増大の産生組織を同定することを目的とした。
老齢マウスとして、加齢促進モデルマウスであるSAMP1マウスの38週齢を老齢有酸素性トレーニング群および老齢安静対照群に分割した。さらに、加齢の影響を検討するために、13週齢のSAMP1マウスを若年安静対照群として用いた。12週間後に、先行研究において報告されているadropinの発現部位(脳、肝臓、腎臓、肺、心臓、脾臓、骨格筋、小腸、白色脂肪、褐色脂肪、血管) を摘出し、各組織の遺伝子発現量を比較検討した。
結果として、加齢により低下するが有酸素性トレーニングによって増加改善するといった血液中と同じ動態は、血管において示された。また、有酸素性トレーニングによる動脈血管のadropin分泌の増大がNO産生を増大するシグナル経路を検討したところ、動脈血管のVEGFR2-protein kinase b(Akt)-endothelial NO synthase(eNOS)シグナル経路の活性化を介してNO産生を増大させた。
したがって、本研究の結果から、高齢者における有酸素性トレーニングによる血中adropin濃度の増大を反映している分泌組織は血管である可能性を示し、有酸素性トレーニングによる動脈血管のadropin分泌の増大が動脈血管のVEGFR2-Akt-eNOSシグナル経路の活性化を介してNO産生を増大させることも明らかにした。

Research Progress Status

翌年度、交付申請を辞退するため、記入しない。

Strategy for Future Research Activity

翌年度、交付申請を辞退するため、記入しない。

Research Products

• [Int'l Joint Research] University of Missouri (ミズーリ大学)(米国)
• [Journal Article] Increased serum salusin-alpha by aerobic exercise training correlates with improvements in arterial stiffness in middle-aged and older adults (2020)
  • Author(s): Fujie Shumpei、Hasegawa Natsuki、Sanada Kiyoshi、Hamaoka Takafumi、Maeda Seiji、Padilla Jaume、Martinez-Lemus Luis A.、Iemitsu Motoyuki
  • Journal Title: Aging Volume: 12 Issue: 2 Pages: 1201-1212
  • DOI: 10.18632/aging.102678
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aerobic exercise training-induced irisin secretion is associated with the reduction of arterial stiffness via nitric oxide production in adults with obesity. (2019)
  • Author(s): Inoue K, Fujie S, Hasegawa N, Horii N, Uchida M, Iemitsu K, Sanada K, Hamaoka T, Iemitsu M.
  • Journal Title: Appl Physiol Nutr Metab Volume: - Issue: 7 Pages: 715-722
  • DOI: 10.1139/apnm-2019-0602
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sexual Dimorphism in Obesity-Associated Endothelial ENaC Activity and Stiffening in Mice. (2019)
  • Author(s): Padilla J, Woodford ML, Lastra-Gonzalez G, Martinez-Diaz V, Fujie S, Yang Y, Lising AMC, Ramirez-Perez FI, Aroor AR, Morales-Quinones M, Ghiarone T, Whaley-Connell A, Martinez-Lemus LA, Hill MA, Manrique-Acevedo C.
  • Journal Title: Endocrinology. Volume: 160 Issue: 12 Pages: 2918-2928
  • DOI: 10.1210/en.2019-00483
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Aging-induced elevation in circulating complement C1q level is associated with arterial stiffness (2019)
  • Author(s): Hasegawa Natsuki、Fujie Shumpei、Horii Naoki、Uchida Masataka、Toyama Yuta、Inoue Kenichiro、Sanada Kiyoshi、Hamaoka Takafumi、Iemitsu Motoyuki
  • Journal Title: Experimental Gerontology Volume: 124 Pages: 110650-110650
  • DOI: 10.1016/j.exger.2019.110650
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of combination of chlorella intake and aerobic exercise training on glycemic control in type 2 diabetic rats (2019)
  • Author(s): Horii Naoki、Hasegawa Natsuki、Fujie Shumpei、Uchida Masataka、Iemitsu Keiko、Inoue Kenichiro、Iemitsu Motoyuki
  • Journal Title: Nutrition Volume: 63-64 Pages: 45-50
  • DOI: 10.1016/j.nut.2019.01.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anti-aging effects for arteriosclerosis by exercise and nutrition. (2019)
  • Author(s): Fujie S, Iemitsu M.
  • Journal Title: Glycative Stress Research Volume: 6 Issue: 4 Pages: 219-226
  • DOI: 10.24659/gsr.6.4_219
  • NAID: 130007805146
  • ISSN: 2188-3602, 2188-3610
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gene expression profile of muscle adaptation to high-intensity intermittent exercise training in young men (2018)
  • Author(s): Miyamoto-Mikami E, Tsuji K, Horii N, Hasegawa N, Fujie S, Homma T, Uchida M, Hamaoka T, Kanehisa H, Tabata I, Iemitsu M
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 16811-16811
  • DOI: 10.1038/s41598-018-35115-x
  • Peer Reviewed / Open Access
• [Journal Article] Resistance training prevents muscle fibrosis and atrophy via down-regulation of C1q-induced Wnt signaling in senescent mice. (2018)
  • Author(s): Horii N, Uchida M, Hasegawa N, Fujie S, Oyanagi E, Yano H, Hashimoto T, Iemitsu M.
  • Journal Title: FASEB J Volume: - Issue: 7 Pages: 3547-3559
  • DOI: 10.1096/fj.201700772rrr
  • Peer Reviewed
• [Journal Article] Effects of different exercise modes on arterial stiffness and nitric oxide synthesis. (2018)
  • Author(s): Hasegawa N, Fujie S, Horii N, Miyamoto-Mikami E, Tsuji K, Uchida M, Hamaoka T, Tabata I, Iemitsu M.
  • Journal Title: Med Sci Sports Exerc Volume: - Issue: 6 Pages: 1177-1185
  • DOI: 10.1249/mss.0000000000001567
  • Peer Reviewed
• [Journal Article] 肥満ラットの有酸素性トレーニングによる動脈血管のapelin産生の増加は内皮型一酸化窒素合成酵素の活性に影響する. (2018)
  • Author(s): 井上健一郎, 藤江隼平, 長谷川夏輝, 堀居直希, 内田昌孝, 佐藤幸治, 家光素行
  • Journal Title: 京都滋賀体育学研究. Volume: 34 Pages: 20-28
  • NAID: 130007970074
  • Peer Reviewed
• [Presentation] Time course of improvement in secretory unbalance of asymmetric dimethylarginine and nitric oxide productions in response to exercise training in middle-aged and older adults. (2019)
  • Author(s): Fujie S, Hasegawa N, Sanada K, Hamaoka T, Maeda S, Iemitsu M.
  • Organizer: European Society of Cardiology Asia with APSC & AFC 2019
  • Int'l Joint Research
• [Presentation] Short time and short term of high-intensity intermittent exercise training reduces arterial stiffness via upregulation of endothelial nitric oxide signalling (2019)
  • Author(s): Hasegawa N, Fujie S, Horii N, Uchida M, Iemitsu M.
  • Organizer: European Society of Cardiology Congress 2020
  • Int'l Joint Research
• [Presentation] Changes in arterial adropin levels by age and aerobic training is related to arterial vasodilation (2019)
  • Author(s): Fujie S, Hasegawa N, Horii N, Uchida M, Maeda S, Jaume Padilla J, Martinez-Lemus LA, Iemitsu M.
  • Organizer: American College of Sports Medicine 66th Annual Meeting
  • Int'l Joint Research
• [Presentation] Effects of carbonated sports drink intake after high-intensity exercise on fatigue recovery in athletic sprinters (2019)
  • Author(s): Hasegawa N, Fujie S, Horii N, Hamaoka T, Iemitsu M.
  • Organizer: American College of Sports Medicine 66th Annual Meeting
  • Int'l Joint Research
• [Presentation] Effect of musclin on aerobic training-induced reduction of arterial stiffness in obese rats (2019)
  • Author(s): Toyama Y, Hasegawa N, Horii N, Inoue K, Iemitsu K, Fujie S, Uchida M, Iemitsu M.
  • Organizer: American College of Sports Medicine 66th Annual Meeting
  • Int'l Joint Research
• [Presentation] Effects of collagen gene polymorphisms on tendon and ligament inflammations in Japanese male endurance athletes. (2019)
  • Author(s): Numa A, Iemitsu K, Fujie S, Hasegawa N, Horii N, Uchida M, Tabata I, Shinohara Y, Iemitsu M.
  • Organizer: American College of Sports Medicine 66th Annual Meeting
  • Int'l Joint Research
• [Presentation] Aerobic training-induced increase in follistatin-like 1 secretion is associated with eNOS phosphorylation in diabetic rats (2019)
  • Author(s): Inoue K, Hasegawa N, Fujie S, Horii N, Uchida M, Iemitsu M.
  • Organizer: American College of Sports Medicine 66th Annual Meeting
  • Int'l Joint Research
• [Presentation] 老齢マウスの有酸素性トレーニングは動脈血管のadropin分泌の促進を介して 血管内皮機能を改善する (2019)
  • Author(s): 藤江隼平、長谷川夏輝、堀居直希、内田昌孝、Padilla Jaume、Martinez-Lemus A. Luis、前田清司、家光素行
  • Organizer: 第74回日本体力医学会大会
• [Presentation] 有酸素性トレーニングによる局所の脂肪組織からのアディポネクチン分泌の亢進が動脈機能に及ぼす影響 (2019)
  • Author(s): 長谷川夏輝、藤江隼平、堀居直希、内田昌孝、家光恵子、外山雄大、井上健一郎、浜岡隆文、家光素行
  • Organizer: 第74回日本体力医学会大会
• [Presentation] 老齢マウスにおける習慣的なレジスタンス運動が筋線維タイプ別の C1q遺伝子発現に及ぼす影響 (2019)
  • Author(s): 堀居直希、内田昌孝、長谷川夏輝、藤江隼平、小柳えり、矢野博己、家光素行
  • Organizer: 第74回日本体力医学会大会
• [Presentation] 有酸素性トレーニングによる持久性能力亢進に対する腸内細菌叢の影響 (2019)
  • Author(s): 内田昌孝、堀居直希、長谷川夏輝、藤江隼平、小柳えり、矢野博己、家光素行
  • Organizer: 第74回日本体力医学会大会
• [Presentation] Salusin-α is a novel biomarker of cardiovascular disease risk in aging and exercise lifestyle: Cross-Sectional and Intervention Study (2019)
  • Author(s): Fujie S, Hasegawa N, Sanada K, Hamaoka T, Maeda S, Padilla J, Martinez-Lemus LA, Iemitsu M.
  • Organizer: Epidemiology and Prevention | Lifestyle and Cardiometabolic Health 2019 Scientific Sessions
  • Int'l Joint Research
• [Presentation] Habitual aerobic exercise-induced decrease in circulating C1q level is associated with reduction of cardiovascular diseases risks in the elderly. (2019)
  • Author(s): Hasegawa N, Horii N, Fujie S, Uchida M, Sanada K, Hamaoka T, Iemitsu M.
  • Organizer: Epidemiology and Prevention | Lifestyle and Cardiometabolic Health 2019 Scientific Sessions
  • Int'l Joint Research
• [Presentation] Chlorella intake prevents aging-induced muscle atrophy and fibrosis in senescent mice. (2018)
  • Author(s): Horii N, Uchida M, Hasegawa N, Fujie S, Mizoguchi T, Okumura E, Sanada K, Iemitsu M.
  • Organizer: 11th international SCWD conference on cachexia, sarcopenia and muscle wasting
  • Int'l Joint Research
• [Presentation] Serum C1q level is a novel biomarker of cardiovascular diseases risk (2018)
  • Author(s): Hasegawa N, Horii N, Fujie S, Uchida M, Sanada K, Hamaoka T, Iemitsu M.
  • Organizer: 11th international SCWD conference on cachexia, sarcopenia and muscle wasting
  • Int'l Joint Research
• [Presentation] Aerobic exercise training-induced increase in muscle-derived Follistatin-like 1 (FSTL1) secretion is associated with nitric oxide production in type 2 diabetic rats. (2018)
  • Author(s): Inoue K, Hasegawa N, Fujie S, Horii N, Uchida M, Iemitsu M.
  • Organizer: American Heart Association scientific sessions 2018
  • Int'l Joint Research
• [Presentation] Elevation of arterial adropin secretion by aerobic exercise training is related to vasodilation via increase in nitric oxide production in aged mice. (2018)
  • Author(s): Fujie S, Hasegawa N, Horii N, Uchida M, Maeda S, Iemitsu M.
  • Organizer: American Heart Association scientific sessions 2018
  • Int'l Joint Research
• [Presentation] Aerobic exercise training-induced changes in anti-inflammatory adipokines secretion from local source are related to reduction of arterial stiffness in elderly. (2018)
  • Author(s): Hasegawa N, Fujie S, Horii N, Uchida M, Iemitsu K, Sanada K, Hamaoka T, Iemitsu M.
  • Organizer: American Heart Association scientific sessions 2018
  • Int'l Joint Research
• [Presentation] Attenuation of NPR-C binding with muscle-derived musclin is related to reduced cardiovascular disease risks by aerobic exercise training in type 2 diabetic rats. (2018)
  • Author(s): Toyama Y, Hasegawa N, Horii N, Inoue K, Iemitsu K, Fujie S, Uchida M, Iemitsu M.
  • Organizer: American Heart Association scientific sessions 2018
  • Int'l Joint Research
• [Presentation] Activation of protein synthesis signaling via increase in muscle 5α-dihydrotestosterone by acute resistance exercise affects muscle hypertrophy in type 2 diabetic rats. (2018)
  • Author(s): Horii N, Hasegawa N, Fujie S, Uchida M, Inoue K, Iemitsu M.
  • Organizer: 23rd annual congress of the European College of Sport Science
  • Int'l Joint Research
• [Presentation] Effect of aerobic training-induced acceleration of adiponectin secretion from local fat cells on arterial stiffness in elderly. (2018)
  • Author(s): Hasegawa N, Fujie S, Horii N, Uchida M, Sanada K, Hamaoka T, Iemitsu M.
  • Organizer: 23rd annual congress of the European College of Sport Science
  • Int'l Joint Research
• [Presentation] Resistance training-induced decrease in circulating C1q is associated with attenuated muscle degradation in senescent mice. (2018)
  • Author(s): Horii N, Uchida M, Hasegawa N, Fujie S, Oyanagi E, Yano H, Hashimoto T, Iemitsu M.
  • Organizer: American College of Sports Medicine 65th Annual Meeting
  • Int'l Joint Research
• [Presentation] Chlorella intake further enhances anaerobic and aerobic capacities increased by high intensity intermittent training. (2018)
  • Author(s): Fujie S, Hasegawa N, Horii N, Oshiden M, Tsuji K, Xu Y, Mizoguchi T, Okumura E, Tabata I, Iemitsu M.
  • Organizer: American College of Sports Medicine 65th Annual Meeting
  • Int'l Joint Research
• [Presentation] Different responses of arterial stiffness and nitric oxide bioavailability to different exercise training programs. (2018)
  • Author(s): Hasegawa N, Fujie S, Horii N, Miyamoto-Mikami E, Tsuji K, Uchida M, Hamaoka T, Tabata I, Iemitsu M.
  • Organizer: American College of Sports Medicine 65th Annual Meeting
  • Int'l Joint Research
• [Presentation] Increased serum irisin level by aerobic training is involved in NO production in obese rats. (2018)
  • Author(s): Inoue K, Fujie S, Hasegawa N, Horii N, Sanada K, Hamaoka T, Iemitsu M.
  • Organizer: American College of Sports Medicine 65th Annual Meeting
  • Int'l Joint Research
• [Presentation] レジスタンス運動が加齢に伴い増大する組織中のC1q遺伝子発現に及ぼす影響. (2018)
  • Author(s): 堀居直希, 内田昌孝, 長谷川夏輝, 藤江隼平, 小柳えり, 矢野博己, 家光素行.
  • Organizer: 第73回日本体力医学会大会
• [Presentation] 老齢マウスの有酸素性トレーニングは脂肪組織のCTRP3遺伝子発現を増大させる. (2018)
  • Author(s): 長谷川夏輝, 藤江隼平, 堀居直希, 内田昌孝, 家光恵子, 浜岡隆文, 家光素行.
  • Organizer: 第73回日本体力医学会大会
• [Presentation] P2X7遺伝子多型が日本人長距離選手における疲労骨折の発生頻度の個人差に及ぼす影響. (2018)
  • Author(s): 沼綾美, 家光恵子, 藤江隼平, 長谷川夏輝, 堀居直希, 内田昌孝, 田畑泉, 篠原靖司, 家光素行.
  • Organizer: 第73回日本体力医学会大会
• [Presentation] 肥満型糖尿病ラットの有酸素性トレーニングは動脈血管のAktとAMPKシグナル伝達経路を活性させる. (2018)
  • Author(s): 井上健一郎, 藤江隼平, 長谷川夏輝, 堀居直希, 家光恵子, 内田昌孝, 家光素行.
  • Organizer: 第73回日本体力医学会大会
• [Presentation] 長期的なクロレラ摂取が異なる運動様式のパフォーマンスに及ぼす影響. (2018)
  • Author(s): 奥村衣梨, 堀居直希, 長谷川夏輝, 藤江隼平, 内田昌孝, 溝口享, 家光素行.
  • Organizer: 日本スポーツ栄養学会第5回大会
• [Presentation] 加齢に伴い増大する組織中のC1q遺伝子発現は習慣的なレジスタンス運動により抑制される. (2018)
  • Author(s): 堀居直希, 内田昌孝, 長谷川夏輝, 藤江隼平, 小柳えり, 矢野博己, 家光素行.
  • Organizer: 第18回日本抗加齢医学会総会