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

• Project/Area Number: 19H04065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Waseda University
• Principal Investigator: Tanisawa Kumpei 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
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2019: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: マイオカイン / 心血管代謝リスク / 骨格筋量 / 体力 / ゲノムワイド関連解析 / メンデルランダム化解析 / 遺伝子バリアント / 筋量 / 筋量・体力

Outline of Research at the Start

骨格筋から分泌されるマイオカインは、運動の様々な恩恵を媒介する因子として注目を集めている。しかし、ヒトにおいて血中マイオカイン濃度が筋量・体力に依存して決定されるというエビデンスは乏しく、本当に心血管代謝リスク因子や疾患発症に影響を及ぼすかどうかも明らかではない。そこで本研究は、精度高く筋量・体力を評価している1500名規模のコホートを用いて、ヒトにおいて筋量・体力と真に関連するマイオカインを明らかにした上で、ゲノムワイド関連解析によるマイオカイン関連遺伝子多型の同定やメンデルランダム化解析等を通じて、マイオカインと心血管代謝リスク因子および疾患発症との因果関係を解明することを目的として行う。

Outline of Final Research Achievements

In the present study, we assessed causal relationships between serum levels of skeletal-muscle- and fitness-related myokines and cardiometabolic risk factors using a Mendelian randomization analysis in 939 middle-aged and elderly men and women. We revealed that fasting serum levels of myokines X, Y, Z that were analyzed in the present study, were negatively correlated with skeletal mass index, and that higher serum levels of these myokines were associated with higher cardiometabolic risks. Furthermore, we explored single nucleotide polymorphisms (SNPs) associated with these myokine levels using a genome-wide association study and performed Mendelian randomization analyses using the SNPs that were associated with serum myokine levels. The Mendelian randomization analyses suggested the causal relationships of myokines X and Z with several cardiometabolic risk factors.

Academic Significance and Societal Importance of the Research Achievements

運動の多岐に渡る恩恵を媒介する因子として、骨格筋から分泌されるマイオカインが注目を集めている。しかし、マイオカインの効果を報告した研究のほとんどは細胞・動物レベルの研究であり、ヒトにおけるエビデンスが不足している。したがって、ヒトを対象とした研究により血清マイオカイン濃度と心血管代謝リスク因子の関連についてエビデンスを提供することは、学術的・社会的に意義があると考えられる。

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) Issue: 1 Pages: 626-626
  • DOI: 10.1186/s12889-022-12971-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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 Daiki、Murakami Haruka、Gando Yuko、Kawakami Ryoko、Tanisawa Kumpei、Ohno Harumi、Konishi Kana、Sasaki Azusa、Morishita Akie、Miyatake Nobuyuki、Miyachi Motohiko
  • Journal Title: Frontiers in Nutrition Volume: 9 Pages: 753127-753127
  • 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: 779967-779967
  • DOI: 10.3389/fnut.2022.779967
  • 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 Issue: 1 Pages: 133-133
  • DOI: 10.1186/s13102-021-00360-7
  • Peer Reviewed / Open Access
• [Journal Article] Association Between Dietary Patterns and Different Metabolic Phenotypes in Japanese Adults: WASEDA'S Health Study (2021)
  • 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: Clin Nutr Volume: 40(11) Issue: 11 Pages: 5523-5530
  • DOI: 10.1016/j.clnu.2021.09.032
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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) Issue: 11 Pages: 2237-2250
  • DOI: 10.1007/s40279-021-01543-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between alcohol dietary pattern and prevalence of dyslipidaemia: WASEDA'S Health Study (2021)
  • 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: - Issue: 11 Pages: 1712-1722
  • DOI: 10.1017/s0007114521002671
  • Peer Reviewed / Open Access
• [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) Issue: 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: - Issue: 1 Pages: 5566880-5566880
  • 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 Daiki、Murakami Haruka、Ohno Harumi、Tanisawa Kumpei、Konishi Kana、Todoroki-Mori Kikue、Tsunematsu Yuta、Sato Michio、Ogata Yuji、Miyoshi Noriyuki、Kubota Naoto、Kunisawa Jun、Wakabayashi Keiji、Kubota Tetsuya、Watanabe Kenji、Miyachi Motohiko
  • Journal Title: BMC Microbiology Volume: 21 Issue: 1 Pages: 196-196
  • 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) Issue: 23 Pages: 151-151
  • 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) Issue: 2 Pages: e001041-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) Issue: 7 Pages: 1855-1864
  • DOI: 10.1007/s40279-021-01451-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Female Athletes Genetically Susceptible to Fatigue Fracture Are Resistant to Muscle Injury (2021)
  • Author(s): Miyamoto-Mikami E, Kumagai H, Tanisawa K, Taga Y, Hirata K, Kikuchi N, Kamiya N, Kawakami R, Midorikawa T, Kawamura T, Kakigi R, Natsume T, Zempo H, Suzuki K, Kohmura Y, Mizuno K, Torii S, Sakamoto S, Oka K, Higuchi M, Naito H, Miyamoto N, Fuku N
  • Journal Title: Medicine & Science in Sports & Exercise Volume: Publish Ahead of Print Issue: 9 Pages: 0-0
  • DOI: 10.1249/mss.0000000000002658
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MANTA, an integrative database and analysis platform that relates microbiome and phenotypic data (2020)
  • Author(s): Chen YA, Park J, Natsume-Kitatani Y, Kawashima H, Mohsen A, Hosomi K, Tanisawa K, Ohno H, Konishi K, Murakami H, Miyachi M, Kunisawa J, Mizuguchi K
  • Journal Title: PLoS One Volume: 15(12) Issue: 12 Pages: e0243609-e0243609
  • DOI: 10.1371/journal.pone.0243609
  • Peer Reviewed / Open Access
• [Journal Article] Visceral fat and cardiorespiratory fitness with prevalence of pre-diabetes/diabetes mellitus among middle-aged and elderly Japanese people: WASEDA’S Health Study (2020)
  • Author(s): Usui Chiyoko、Kawakami Ryoko、Tanisawa Kumpei、Ito Tomoko、Tabata Hiroki、Iizuka Satoshi、Kawamura Takuji、Midorikawa Taishi、Sawada Susumu S.、Torii Suguru、Sakamoto Shizuo、Suzuki Katsuhiko、Ishii Kaori、Oka Koichiro、Muraoka Isao、Higuchi Mitsuru
  • Journal Title: PLOS ONE Volume: 15 Issue: 10 Pages: 0241018-0241018
  • DOI: 10.1371/journal.pone.0241018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between dietary intake and the prevalence of tumourigenic bacteria in the gut microbiota of middle-aged Japanese adults (2020)
  • Author(s): Watanabe Daiki、Murakami Haruka、Ohno Harumi、Tanisawa Kumpei、Konishi Kana、Tsunematsu Yuta、Sato Michio、Miyoshi Noriyuki、Wakabayashi Keiji、Watanabe Kenji、Miyachi Motohiko
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 15221-15221
  • DOI: 10.1038/s41598-020-72245-7
  • Peer Reviewed / Open Access
• [Journal Article] Cut‐offs for calf circumference as a screening tool for low muscle mass: WASEDA'S Health Study (2020)
  • Author(s): Kawakami Ryoko、Miyachi Motohiko、Sawada Susumu S.、Torii Suguru、Midorikawa Taishi、Tanisawa Kumpei、Ito Tomoko、Usui Chiyoko、Ishii Kaori、Suzuki Katsuhiko、Sakamoto Shizuo、Higuchi Mitsuru、Muraoka Isao、Oka Koichiro
  • Journal Title: Geriatrics & Gerontology International Volume: 20 Issue: 10 Pages: 943-950
  • DOI: 10.1111/ggi.14025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sport and Exercise Genomics: The FIMS 2019 Consensus Statement Update (2020)
  • Author(s): Tanisawa K, Wang G, Seto J, Verdouka I, Twycross-Lewis R, Karanikolou A, Tanaka M, Borjesson M, Di Luigi L, Dohi M, Wolfarth B, Swart J, Bilzon JLJ, Badtieva V, Papadopoulou T, Casasco M, Geistlinger M, Bachl N, Pigozzi F, Pitsiladis Y
  • Journal Title: Br J Sports Med Volume: 54(16) Issue: 16 Pages: 969-975
  • DOI: 10.1136/bjsports-2019-101532
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Micronutrient Intake Adequacy in Men and Women with a Healthy Japanese Dietary Pattern (2019)
  • Author(s): Ito T, Tanisawa K, Kawakami R, Usui C, Ishii K, Suzuki K, Sakamoto S, Muraoka I, Oka K, Higuchi M
  • Journal Title: Nutrients Volume: 12(1) Issue: 1 Pages: 6-6
  • DOI: 10.3390/nu12010006
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Vitamin D Supplementation on Body Composition and Physical Fitness in Healthy Adults: A Double-Blind, Randomized Controlled Trial (2019)
  • Author(s): Sun X, Tanisawa K, Zhang Y, Ito T, Oshima S, Higuchi M, Cao ZB
  • Journal Title: Ann Nutr Metab Volume: 75(4) Pages: 231-237
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ageing Affects the Association Between Serum 25- Hydroxyvitamin D Concentrations and Cardiorespiratory Fitness in Middle-Aged and Elderly Men (2019)
  • Author(s): Sun X, Tanisawa K, Ito T, Oshima S, Higuchi M, Cao ZB
  • Journal Title: Asia Pac J Clin Nutr Volume: 28(3) Pages: 614-620
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Renormalized Basal Metabolic Rate Describes the Human Aging Process and Longevity (2019)
  • Author(s): Kitazoe Y, Kishino H, Tanisawa K, Udaka K, Tanaka M
  • Journal Title: Aging Cell Volume: 18(4) Issue: 4 Pages: 1-11
  • DOI: 10.1111/acel.12968
  • Peer Reviewed / Open Access / Int'l Joint Research