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Reply to ‘Lactate as a major myokine and exerkine’

Nature Reviews Endocrinology volume 18, page 713 (2022)Cite this article

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We appreciate the commentary on our Review (Chow, L.S. et al. Exerkines in health, resilience and disease. Nat. Rev. Endocrinol. 18, 273–289 (2022))1 by George Brooks and colleagues regarding lactate as a major myokine and exerkine (Brooks, G. A. et al. Lactate as a major myokine and exerkine. Nat. Rev. Endocrinol. https://doi.org/10.1038/s41574-022-00724-0 (2022)2). In our Review1, we mentioned that lactate is a recognized myokine, whose role beyond serving as an energy source to mediate exercise-related effects is increasingly recognized3. Lactate can mediate tissue-to-tissue communication during exercise. The effect of lactate can be autocrine, as exemplified by lactate enhancing the myogenesis of C2C12 cells4. Alternatively, lactate can act in a paracrine or endocrine fashion, as exemplified by stimulation of TGFβ2 release from human adipocytes5, or by activation of CD8+ lymphocytes in a mouse model to delay tumour growth across multiple cancer types6.

We recognize that our Review1 primarily described lactate as an exerkine with direct signalling effects; this description was in the spirit of staying consistent with the direct-signalling descriptions of other exerkines. Notably, a 2022 Nature paper described exercise-stimulated synthesis of N-lactoyl-phenylalanine (Lac-Phe) as an important exerkine that suppressed feeding and reduced obesity7. The commentary by Brooks et al.2 further describes lactate’s metabolic effects in driving exercise-induced adaptions. This expansion is welcome, as Brooks describes lactate serving as a ‘fulcrum of metabolism’ in a 2020 Review8. Lactate has an integral role in the exercise response and a more fleshed-out description of its impact, beyond direct signalling, upholds its valuable contributions.

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References

  1. Chow, L. S. et al. Exerkines in health, resilience and disease. Nat. Rev. Endocrinol. 18, 273–289 (2022).

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Authors and Affiliations

  1. Division of Diabetes Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA

    Lisa S. Chow

  2. Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Robert E. Gerszten & Jeremy M. Robbins

  3. Department of Pathology, McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA

    Joan M. Taylor

  4. Centre of Inflammation and Metabolism/Centre for PA Research (CIM/CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Bente K. Pedersen

  5. Stiles-Nicholson Brain institute and Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL, USA

    Henriette van Praag

  6. Human Performance Laboratory, Ball State University, Muncie, IN, USA

    Scott Trappe

  7. Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

    Mark A. Febbraio

  8. Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Zorina S. Galis & Yunling Gao

  9. School of Kinesiology, University of Michigan, Ann Arbor, MI, USA

    Jacob M. Haus

  10. Division of Endocrinology, Nutrition, and Metabolism, Mayo Clinic College of Medicine and Science, Rochester, MN, USA

    Ian R. Lanza

  11. Division of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School-the University of Queensland School of Medicine, New Orleans, LA, USA

    Carl J. Lavie

  12. Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Chih-Hao Lee

  13. Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain

    Alejandro Lucia

  14. Research Institute Hospital 12 de Octubre (‘imas12’), Madrid, Spain

    Alejandro Lucia

  15. CIBER en Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain

    Alejandro Lucia

  16. Institute of Metabolic and Cardiovascular Diseases, Team MetaDiab, Inserm UMR1297, Toulouse, France

    Cedric Moro

  17. Toulouse III University - Paul Sabatier (UPS), Toulouse, France

    Cedric Moro

  18. Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA

    Ambarish Pandey

  19. Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA

    Kristin I. Stanford

  20. National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK

    Alice E. Thackray

  21. Department of Anatomy, University of California San Francisco, San Francisco, CA, USA

    Saul Villeda

  22. Department of Anatomy and Physiology, School of Biomedical Sciences, The University of Melbourne, Victoria, Australia

    Matthew J. Watt

  23. Division of Diabetes, Endocrinology, & Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Ashley Xia

  24. Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden

    Juleen R. Zierath

  25. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Juleen R. Zierath

  26. Translational Research Institute, AdventHealth, Orlando, FL, USA

    Bret H. Goodpaster

  27. Department of Genetics, Stanford School of Medicine, Stanford, CA, USA

    Michael Snyder

Authors
  1. Lisa S. Chow
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  2. Robert E. Gerszten
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  3. Joan M. Taylor
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  10. Jacob M. Haus
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  11. Ian R. Lanza
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  21. Matthew J. Watt
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  22. Ashley Xia
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  23. Juleen R. Zierath
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  24. Bret H. Goodpaster
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  25. Michael Snyder
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Corresponding authors

Correspondence to Lisa S. Chow, Bret H. Goodpaster or Michael Snyder.

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Competing interests

L.S.C. has a Dexcom investigator initiated grant: product only. C.J.L. acts as a consultant for PAIhealth on their Personalized Activity Intelligence applications. A.P. is on an advisory board of Roche Diagnostics. M.P.S. is a Cofounder and scientific advisory board member of Personalis, SensOmics, Qbio, January, Filtricine, Protos, NiMo and Mirvie. He is also an advisor for Genapsys. The other authors declare no competing interests.

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Chow, L.S., Gerszten, R.E., Taylor, J.M. et al. Reply to ‘Lactate as a major myokine and exerkine’. Nat Rev Endocrinol 18, 713 (2022). https://doi.org/10.1038/s41574-022-00726-y

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