Exerkines in health, resilience and disease

Lisa S. Chow, Robert E. Gerszten, Joan M. Taylor, Bente K. Pedersen, Henriette van Praag, Scott Trappe, Mark A. Febbraio, Zorina S. Galis, Yunling Gao, Jacob M. Haus, Ian R. Lanza, Carl J. Lavie, Chih Hao Lee, Alejandro Lucia, Cedric Moro, Ambarish Pandey, Jeremy M. Robbins, Kristin I. Stanford, Alice E. Thackray, Saul VilledaMatthew J. Watt, Ashley Xia, Juleen R. Zierath, Bret H. Goodpaster, Michael P. Snyder

Research output: Contribution to journalReview articlepeer-review

403 Scopus citations

Abstract

The health benefits of exercise are well-recognized and are observed across multiple organ systems. These beneficial effects enhance overall resilience, healthspan and longevity. The molecular mechanisms that underlie the beneficial effects of exercise, however, remain poorly understood. Since the discovery in 2000 that muscle contraction releases IL-6, the number of exercise-associated signalling molecules that have been identified has multiplied. Exerkines are defined as signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways. A multitude of organs, cells and tissues release these factors, including skeletal muscle (myokines), the heart (cardiokines), liver (hepatokines), white adipose tissue (adipokines), brown adipose tissue (baptokines) and neurons (neurokines). Exerkines have potential roles in improving cardiovascular, metabolic, immune and neurological health. As such, exerkines have potential for the treatment of cardiovascular disease, type 2 diabetes mellitus and obesity, and possibly in the facilitation of healthy ageing. This Review summarizes the importance and current state of exerkine research, prevailing challenges and future directions.

Original languageEnglish (US)
Pages (from-to)273-289
Number of pages17
JournalNature Reviews Endocrinology
Volume18
Issue number5
DOIs
StatePublished - May 2022

Bibliographical note

Funding Information:
The authors thank A. Honkala (Stanford University) and N. C. Oldenburg (University of Minnesota) for their assistance with the manuscript. The workshop that set the foundation for this Review article was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH). The listed authors acknowledge the support of the following grants. L.S.C.: NIH grant R01DK098203; B.H.G.: NIH grant U01AR071133; A.L.: Spanish Ministry of Economy and Competitiveness and Fondos FEDER (PI18/00139); C.M.: European Federation of the Study of Diabetes/MSD, Occitanie Region/FEDER funds (DIABKINES, MP0021755 and Enterosys); B.K.P.: TrygFonden for the Centre for PA Research (CFAS); A.P.: Texas Health Resources Clinical Scholarship, Gilead Sciences Research Scholar Program, NIH National Institute of Aging GEMSSTAR grant (1R03AG067960-01), and Applied Therapeutics; J.M.R.: NIH grant HL150327-01A1; H.v.P.: NIH National Institute on Aging (NIA)/NIH IRP and the FDOH Ed and Ethel Moore Alzheimer’s Disease Research program; K.I.S.: NIH grants R01-HL138738 and R01-AG060542; A.E.T.: National Institute for Health Research (NIHR) Leicester Biomedical Research Centre; J.M.T.: NIH grant 1R01HL142879; S.T.: NIH grants U01AR071133; J.R.Z.: Swedish Research Council for Sport Science (P2018-0097), Swedish Research Council (Vetenskapsrådet) (2015-00165), and Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (NNF18CC0034900); M.P.S.: NIH grants U24DK112348 and U54DK102556. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Funding Information:
The authors thank A. Honkala (Stanford University) and N. C. Oldenburg (University of Minnesota) for their assistance with the manuscript. The workshop that set the foundation for this Review article was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH). The listed authors acknowledge the support of the following grants. L.S.C.: NIH grant R01DK098203; B.H.G.: NIH grant U01AR071133; A.L.: Spanish Ministry of Economy and Competitiveness and Fondos FEDER (PI18/00139); C.M.: European Federation of the Study of Diabetes/MSD, Occitanie Region/FEDER funds (DIABKINES, MP0021755 and Enterosys); B.K.P.: TrygFonden for the Centre for PA Research (CFAS); A.P.: Texas Health Resources Clinical Scholarship, Gilead Sciences Research Scholar Program, NIH National Institute of Aging GEMSSTAR grant (1R03AG067960-01), and Applied Therapeutics; J.M.R.: NIH grant HL150327-01A1; H.v.P.: NIH National Institute on Aging (NIA)/NIH IRP and the FDOH Ed and Ethel Moore Alzheimer’s Disease Research program; K.I.S.: NIH grants R01-HL138738 and R01-AG060542; A.E.T.: National Institute for Health Research (NIHR) Leicester Biomedical Research Centre; J.M.T.: NIH grant 1R01HL142879; S.T.: NIH grants U01AR071133; J.R.Z.: Swedish Research Council for Sport Science (P2018-0097), Swedish Research Council (Vetenskapsrådet) (2015-00165), and Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (NNF18CC0034900); M.P.S.: NIH grants U24DK112348 and U54DK102556. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Publisher Copyright:
© 2022, Springer Nature Limited.

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