Assessing causal relationship of skeletal muscle- and fitness-related myokines with cardiometabolic risk factors

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19H04065
• Research Institution: Waseda University
• Principal Investigator: 谷澤 薫平 早稲田大学, スポーツ科学学術院, 専任講師 (50771812)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: マイオカイン / 骨格筋量 / 遺伝子バリアント / ゲノムワイド関連解析 / メンデルランダム化解析 / 心血管代謝リスク

Outline of Annual Research Achievements

本年度は、昨年度に選定した3つのマイオカインの血清濃度と骨格筋量および心血管代謝リスク因子との関連性を検討した。また、これらのマイオカインの血清濃度を規定する遺伝子バリアントをゲノムワイド関連解析（GWAS）により探索した。
中高齢者939名を対象として、3つのマイオカイン（X、Y、Z）の血清濃度をELISAにより分析し、DXAにより測定した骨格筋指数（四肢除脂肪軟組織量/身長の二乗）との相関を調べた結果、いずれのマイオカインも骨格筋指数と正に相関していた（年齢、性別およびBMIで調整）。また、マイオカインX、YおよびZの血清濃度と心血管代謝リスク因子との相関を調べた結果、収縮期・拡張期血圧および血清中性脂肪濃度はマイオカインXおよびYと正に相関し、血中グルコース濃度とヘモグロビンA1C濃度はマイオカインYおよびZと正に相関していた（年齢、性別およびBMIで調整）。さらに、GWASによりマイオカインX、YおよびZと関連する遺伝子バリアントを探索した。マイオカインXについてはGWASの有意水準（P<5.0×10-8）を満たす遺伝子バリアントはなかったが、マイオカインYおよびZについては、GWASの有意水準を満たす遺伝子バリアントが複数同定された。
以上の結果より、①骨格筋量が多いほどマイオカインX、YおよびZの安静時の血清濃度が高いこと、②これらの血清濃度が高いほど心血管代謝リスクが高いことが示唆された。動物実験により、これら3つのマイオカインは健康に有益な影響をもたらすことが報告されている。このことを考慮すると、インスリン抵抗性やレプチン抵抗性のように、マイオカインの抵抗性が生じた者において、心血管代謝リスク因子が高値を示した可能性がある。また、③マイオカインYおよびZの血清濃度と強く関連する遺伝子バリアントが複数同定された。今後、再現性の検討を行った上で、これらを用いたメンデルランダム化解析を進め、因果関係の推定を試みる。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] The combination of cardiorespiratory fitness and muscular fitness, and prevalence of diabetes mellitus in middle-aged and older men: WASEDA'S Health Study (2022)
  • Author(s): Wang D, Sawada SS, Tabata H, Kawakami R, Ito T, Tanisawa K, Higuchi M, Ishii K, Oka K, Suzuki K, Sakamoto S
  • Journal Title: BMC Public Health Volume: 22(1) Pages: 626
  • DOI: 10.1186/s12889-022-12971-x
  • Peer Reviewed / Open Access
• [Journal Article] Association Between Temporal Changes in Diet Quality and Concurrent Changes in Dietary Intake, Body Mass Index, and Physical Activity Among Japanese Adults: A Longitudinal Study (2022)
  • Author(s): Watanabe D, Murakami H, Gando Y, Kawakami R, Tanisawa K, Ohno H, Konishi K, Sasaki A, Morishita A, Miyatake N, Miyachi M
  • Journal Title: Front Nutr Volume: 9 Pages: 753127
  • DOI: 10.3389/fnut.2022.753127
  • Peer Reviewed / Open Access
• [Journal Article] Association Between Dietary Patterns and Different Metabolic Phenotypes in Japanese Adults: WASEDA'S Health Study (2022)
  • Author(s): Tanisawa K, Ito T, Kawakami R, Usui C, Kawamura T, Suzuki K, Sakamoto S, Ishii K, Muraoka I, Oka K, Higuchi M
  • Journal Title: Front Nutr Volume: 9 Pages: 779967
  • DOI: 10.3389/fnut.2022.779967
  • Peer Reviewed / Open Access
• [Journal Article] Association between alcohol dietary pattern and prevalence of dyslipidaemia: WASEDA'S Health Study (2022)
  • Author(s): Tanisawa K, Ito T, Kawakami R, Usui C, Kawamura T, Suzuki K, Sakamoto S, Ishii K, Muraoka I, Oka K, Higuchi M
  • Journal Title: Br J Nutr Volume: 127(11) Pages: 1712-1722
  • DOI: 10.1017/S0007114521002671
  • Peer Reviewed / Open Access
• [Journal Article] Effect of a 1-year intervention comprising brief counselling sessions and low-dose physical activity recommendations in Japanese adults, and retention of the effect at 2 years: a randomized trial (2021)
  • Author(s): Tripette J, Gando Y, Murakami H, Kawakami R, Tanisawa K, Ohno H, Konishi K, Tanimoto M, Tanaka N, Kawano H, Yamamoto K, Morishita A, Iemitsu M, Sanada K, Miyatake N, Miyachi M
  • Journal Title: BMC Sports Sci Med Rehabil Volume: 13(1) Pages: 133
  • DOI: 10.1186/s13102-021-00360-7
  • Peer Reviewed / Open Access
• [Journal Article] Development and validation of a simple anthropometric equation to predict appendicular skeletal muscle mass. (2021)
  • Author(s): Kawakami R, Miyachi M, Tanisawa K, Ito T, Usui C, Midorikawa T, Torii S, Ishii K, Suzuki K, Sakamoto S, Higuchi M, Muraoka I, Oka K
  • Journal Title: Clin Nutr Volume: 40(11) Pages: 5523-5530
  • DOI: 10.1016/j.clnu.2021.09.032
  • Peer Reviewed / Open Access
• [Journal Article] Establishing a Global Standard for Wearable Devices in Sport and Exercise Medicine: Perspectives from Academic and Industry Stakeholders. (2021)
  • Author(s): Ash GI et al.
  • Journal Title: Sports Med Volume: 51(11) Pages: 2237-2250
  • DOI: 10.1007/s40279-021-01543-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Wearable and telemedicine innovations for Olympic events and elite sport (2021)
  • Author(s): Muniz-Pardos B, Angeloudis K, Guppy FM, Keramitsoglou I, Sutehall S, Bosch A, Tanisawa K, Hosokawa Y, Ash GI, Schobersberger W, Grundstein AJ, Casa DJ, Morrissey MC, Yamasawa F, Zelenkova I, Racinais S, Pitsiladis Y
  • Journal Title: J Sports Med Phys Fitness Volume: 61(8) Pages: 1061-1072
  • DOI: 10.23736/S0022-4707.21.12752-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Determinants of Resting Oxidative Stress in Middle-Aged and Elderly Men and Women: WASEDA'S Health Study (2021)
  • Author(s): Kawamura T, Tanisawa K, Kawakami R, Usui C, Ito T, Tabata H, Nakamura N, Kurosawa S, Choi W, Ma S, Radak Z, Sawada SS, Suzuki K, Ishii K, Sakamoto S, Oka K, Higuchi M, Muraoka I
  • Journal Title: Oxid Med Cell Longev Volume: － Pages: 5566880
  • DOI: 10.1155/2021/5566880
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stool pattern is associated with not only the prevalence of tumorigenic bacteria isolated from fecal matter but also plasma and fecal fatty acids in healthy Japanese adults (2021)
  • Author(s): Watanabe D, Murakami H, Ohno H, Tanisawa K, Konishi K, Todoroki-Mori K, Tsunematsu Y, Sato M, Ogata Y, Miyoshi N, Kubota N, Kunisawa J, Wakabayashi K, Kubota T, Watanabe K, Miyachi M
  • Journal Title: BMC Microbiol Volume: 21(1) Pages: 196
  • DOI: 10.1186/s12866-021-02255-6
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive analysis of gut microbiota of a healthy population and covariates affecting microbial variation in two large Japanese cohorts (2021)
  • Author(s): Park J, Kato K, Murakami H, Hosomi K, Tanisawa K, Nakagata T, Ohno H, Konishi K, Kawashima H, Chen YA, Mohsen A, Xiao JZ, Odamaki T, Kunisawa J, Mizuguchi K, Miyachi M
  • Journal Title: BMC Microbiol Volume: 21(1) Pages: 151
  • DOI: 10.1136/bjsports-2021-104014
  • Peer Reviewed / Open Access
• [Journal Article] Ethical dilemmas and validity issues related to the use of new cooling technologies and early recognition of exertional heat illness in sport (2021)
  • Author(s): Muniz-Pardos B, Angeloudis K, Guppy FM, Tanisawa K, Hosokawa Y, Ash GI, Schobersberger W, Grundstein AJ, Yamasawa F, Racinais S, Casa DJ, Pitsiladis YP
  • Journal Title: BMJ Open Sport Exerc Med Volume: 7(2) Pages: e001041
  • DOI: 10.1136/bmjsem-2021-001041
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021)
  • Author(s): Hamilton BR et al.
  • Journal Title: Sports Med Volume: 53(9) Pages: 1855-1864
  • DOI: 10.1007/s40279-021-01451-8
  • Peer Reviewed / Open Access / Int'l Joint Research