The effect of exercise on metabolic crosstalk between heart and liver

Document Type : Review Articles


1 PhD Candidate of Exercise Physiology, Faculty of Sport Sciences, Islamic Azad University, Karaj, Iran

2 Department of Sport Sciences, Islamic Azad University, Urmia Branch, Urmia, Iran


This research paper delves into the intricate interplay between the heart and liver within the realm of metabolic regulation, focusing on the impact of exercise as a pivotal modulator of this dynamic relationship. Through a comprehensive review of pertinent literature, encompassing peer-reviewed articles, reviews, and meta-analyses sourced from databases such as PubMed, Scopus, and Google Scholar, this paper analyzes the existing understanding of how exercise influences the metabolic crosstalk between the heart and liver. The findings underscore the positive influence of regular physical activity on the metabolic interplay between these vital organs, ultimately contributing to enhanced overall metabolic health. Emphasizing both physiological and molecular aspects, the review provides a succinct overview of its content, highlighting the significance of exercise in modulating metabolic processes. In exploring human studies, animal models, and molecular techniques, this review aims to not only consolidate current knowledge but also to identify research gaps, fostering a foundation for future investigations. The potential therapeutic implications of exercise in mitigating metabolic disorders through the modulation of heart-liver crosstalk are discussed. By addressing inclusion criteria such as studies published within the last decade, written in English, and focusing on human or animal models, this paper contributes to the evolving understanding of the intricate relationship between exercise, heart health, and liver function.

What is already known on this subject?

The existing knowledge on the subject of the effect of exercise on metabolic crosstalk between the heart and liver encompasses several key findings. It is known that exercise induces the release of various signaling molecules, including myokines from skeletal muscle and "exerkines" from the heart, liver, white and brown adipose tissue, and the nervous system. These molecules play a crucial role in inter-organ communication and contribute to the systemic effects of exercise on metabolism and overall health. Additionally, previous research has demonstrated that exercise can impact liver health by influencing liver enzymes, antioxidant systems, and metabolic pathways. Furthermore, the effects of different types of exercise, such as aerobic and resistance training, on cardiovascular risk factors and liver enzymes in various populations, including individuals with dyslipidemia and patients undergoing coronary interventions, have been investigated. This body of knowledge provides a foundation for understanding the complex interplay between exercise, the heart, and the liver, and its implications for metabolic health and disease prevention.

What this study adds?

This research adds to the existing knowledge by providing insights into the impact of exercise on liver enzymes and antioxidant systems, as well as the age-dependent effects of different exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver. It also contributes to understanding the effects of aerobic interval exercise on cardiovascular risk factors and liver enzymes in individuals with dyslipidemia. Furthermore, the study of a home-based exercise intervention's impact on cardiac biomarkers, liver enzymes, and cardiometabolic outcomes in patients after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) provides valuable information on the potential benefits of exercise in a clinical setting (Bernier et al., 2022; Khan et al., 2019; Olgoye et al., 2021; Zolfaghari et al., 2020).


Main Subjects


We thank the anonymous referees for their useful suggestion.



Compliance with ethical standards

Conflict of interest No conflict of interest.

Ethical approval Not applicable.

Informed consent Not applicable.

Author contributions

Conceptualization: A.M; Methodology: A.M; Software: S.Z; Validation: A.M; Formal analysis: S.Z; Investigation: A.M; Resources: A.M; Data curation: S.Z; Writing - original draft: A.M; Writing - review & editing: A.M; Visualization: A.M; Supervision: A.M; Project administration: A.M; Funding acquisition: A.M.

Baskin, K. K., Bookout, A. L., & Olson, E. N. (2014). The heart-liver metabolic axis: defective communication exacerbates disease. EMBO Mol Med, 6(4), 436-438.
Belanger, M. J., Rao, P., & Robbins, J. M. (2022). Exercise, Physical Activity, and Cardiometabolic Health: Pathophysiologic Insights. Cardiol Rev, 30(3), 134-144.
Bernier, M., Enamorado, I. N., Gomez-Cabrera, M. C., Calvo-Rubio, M., Gonzalez-Reyes, J. A., Price, N. L., . . . de Cabo, R. (2022). Age-dependent impact of two exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver of male mice. NPJ Aging, 8(1), 8.
Blackwell, J. A., & Stanford, K. I. (2022). Exercise-induced Inter-tissue Communication: Adipose Tissue & the Heart. Current Opinion in Physiology, 100626.
Brunetta, H. S., & Townsend, L. K. (2022). Muscle-fat crosstalk: effects of exercise on brown adipose tissue; what do we know? J Physiol, 600(17), 4039-4040.
Cao, X., & Thyfault, J. P. (2023). Exercise drives metabolic integration between muscle, adipose and liver metabolism and protects against aging-related diseases. Exp Gerontol, 176, 112178.
Catoire, M., Mensink, M., Kalkhoven, E., Schrauwen, P., & Kersten, S. (2014). Identification of human exercise-induced myokines using secretome analysis. Physiol Genomics, 46(7), 256-267.
Chen, J., Cai, Y., Cong, E., Liu, Y., Gao, J., Li, Y., . . . Flint, J. (2014). Childhood sexual abuse and the development of recurrent major depression in Chinese women. PLoS One, 9(1), e87569.
Colberg, S. R., Sigal, R. J., Fernhall, B., Regensteiner, J. G., Blissmer, B. J., Rubin, R. R., . . . Braun, B. (2010). Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes care, 33(12), e147-e167. 
Deligiannis, A., D'Alessandro, C., & Cupisti, A. (2021). Exercise training in dialysis patients: impact on cardiovascular and skeletal muscle health. Clin Kidney J, 14(Suppl 2), ii25-ii33.
Green, D. J., O'Driscoll, G., Joyner, M. J., & Cable, N. T. (2008). Exercise and cardiovascular risk reduction: time to update the rationale for exercise? J Appl Physiol (1985), 105(2), 766-768.
Grundy, S. M. (2012). Pre-diabetes, metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol, 59(7), 635-643.
Guo, S., Feng, Y., Zhu, X., Zhang, X., Wang, H., Wang, R., . . . Kong, X. (2023). Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis. Nat Commun, 14(1), 6047.
Handschin, C., & Spiegelman, B. M. (2006). Peroxisome proliferator activated receptor γ coactivator 1 coactivators, energy homeostasis, and metabolism. Endocrine reviews, 27(7), 728-735.
Hardie, D. G. (2011). AMP-activated protein kinase—an energy sensor that regulates all aspects of cell function. Genes & development, 25(18), 1895-1908.
Hoene, M., Kappler, L., Kollipara, L., Hu, C., Irmler, M., Bleher, D., . . . Weigert, C. (2021). Exercise prevents fatty liver by modifying the compensatory response of mitochondrial metabolism to excess substrate availability. Mol Metab, 54, 101359.
Johnson, N. A., Keating, S. E., & George, J. (2012). Exercise and the liver: implications for therapy in fatty liver disorders. Seminars in liver disease.
Keating, S. E., Hackett, D. A., Parker, H. M., O'Connor, H. T., Gerofi, J. A., Sainsbury, A., . . . Johnson, N. A. (2015). Effect of aerobic exercise training dose on liver fat and visceral adiposity. J Hepatol, 63(1), 174-182.
Keating, S. E., Sabag, A., Hallsworth, K., Hickman, I. J., Macdonald, G. A., Stine, J. G., . . . Johnson, N. A. (2023). Exercise in the Management of Metabolic-Associated Fatty Liver Disease (MAFLD) in Adults: A Position Statement from Exercise and Sport Science Australia. Sports Med, 53(12), 2347-2371.
Khan, A., Khan, S., Khan, S., Bhatti, S., & Khan, S. (2019). Impact of Low-Intensity Exercise on Liver Enzymes and Antioxidants Systems of the Body. International Journal of Medical Research and Health Sciences, 8, 148-155.
Lavie, C. J., Arena, R., Swift, D. L., Johannsen, N. M., Sui, X., Lee, D. C., . . . Blair, S. N. (2015). Exercise and the cardiovascular system: clinical science and cardiovascular outcomes. Circ Res, 117(2), 207-219.
Magida, J. A., & Leinwand, L. A. (2014). Metabolic crosstalk between the heart and liver impacts familial hypertrophic cardiomyopathy. EMBO Mol Med, 6(4), 482-495.
Martínez-Montoro, J. I., Benítez-Porres, J., Tinahones, F. J., Ortega-Gómez, A., & Murri, M. (2023). Effects of exercise timing on metabolic health. Obesity Reviews, 24(10), e13599.
Miyashita, K., Itoh, H., Tsujimoto, H., Tamura, N., Fukunaga, Y., Sone, M., . . . Nakao, K. (2009). Natriuretic peptides/cGMP/cGMP-dependent protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity. Diabetes, 58(12), 2880-2892.
Montgomery, M. K., De Nardo, W., & Watt, M. J. (2019). Impact of lipotoxicity on tissue “cross talk” and metabolic regulation. Physiology, 34(2), 134-149.
Mounesan, A., & Nourzad, F. (2023). The Effect of Acute active and Passive Cool-Down After Exercise on Changes in Blood Pressure and Heart Rate of Teenage Boy Basketball Players. Research in Sport Sciences Education (RISSE), 1(1), 49-54.
Natarajan, N., Hori, D., Flavahan, S., Steppan, J., Flavahan, N. A., Berkowitz, D. E., & Pluznick, J. L. (2016). Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genomics, 48(11), 826-834.
Nikroo, H., Hosseini, S. R. A., Fathi, M., Sardar, M. A., & Khazaei, M. (2020). The effect of aerobic, resistance, and combined training on PPAR-alpha, SIRT1 gene expression, and insulin resistance in high-fat diet-induced NAFLD male rats. Physiol Behav, 227, 113149.
Olgoye, A. M., Samadi, A., & Jamalian, S. A. (2021). Effects of a home based exercise intervention on cardiac biomarkers, liver enzymes, and cardiometabolic outcomes in CABG and PCI patients. J Res Med Sci, 26, 5.
Pedersen, B. K., & Febbraio, M. A. (2012). Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nature Reviews Endocrinology, 8(8), 457-465.
Perry, R. J., Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2014). The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature, 510(7503), 84-91.
Ratziu, V., Bellentani, S., Cortez-Pinto, H., Day, C., & Marchesini, G. (2010). A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol, 53(2), 372-384.
Rector, R. S., Uptergrove, G. M., Morris, E. M., Borengasser, S. J., Laughlin, M. H., Booth, F. W., . . . Ibdah, J. A. (2011). Daily exercise vs. caloric restriction for prevention of nonalcoholic fatty liver disease in the OLETF rat model. Am J Physiol Gastrointest Liver Physiol, 300(5), G874-883.
Robbins, J. M., & Gerszten, R. E. (2023). Exercise, exerkines, and cardiometabolic health: from individual players to a team sport. J Clin Invest, 133(11).
Rochlani, Y., Pothineni, N. V., Kovelamudi, S., & Mehta, J. L. (2017). Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis, 11(8), 215-225.
Rohrbach, S., Niemann, B., Silber, R. E., & Holtz, J. (2005). Neuregulin receptors erbB2 and erbB4 in failing human myocardium -- depressed expression and attenuated activation. Basic Res Cardiol, 100(3), 240-249.
Sabaratnam, R., Wojtaszewski, J. F. P., & Hojlund, K. (2022). Factors mediating exercise-induced organ crosstalk. Acta Physiol (Oxf), 234(2), e13766.
Sanousi, H. A., & Hashim, A. S. (2021). The Positive Impact of Weight Management on Liver Cirrhosis.
Schok, K., Jasek, J., Wiejak, K., Skoczylas, K., Mikulska, J., & Rokicki, S. (2023). The relationship between hypothyroidism and physical exercise: impact on exercise tolerance and health. Journal of Education, Health and Sport.
Seldin, M. M., Peterson, J. M., Byerly, M. S., Wei, Z., & Wong, G. W. (2012). Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. Journal of Biological Chemistry, 287(15), 11968-11980.
Stefan, N., Haring, H. U., & Cusi, K. (2019). Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol, 7(4), 313-324.
Swarup, S., Goyal, A., & Grigorova, Y. (2023). Metabolic Syndrome [Updated 2022 Oct 24]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
Talabér, G., Jondal, M., & Okret, S. (2013). Extra-adrenal glucocorticoid synthesis: immune regulation and aspects on local organ homeostasis. Molecular and cellular endocrinology, 380(1-2), 89-98.
Tanaka, A., & Node, K. (2020). Crosstalk between the liver and heart: revisited for prevention and treatment. ESC Heart Fail, 7(6), 4489-4490.
Thyfault, J. P., & Bergouignan, A. (2020). Exercise and metabolic health: beyond skeletal muscle. Diabetologia, 63(8), 1464-1474.
Trefts, E., Williams, A. S., & Wasserman, D. H. (2015). Exercise and the Regulation of Hepatic Metabolism. Prog Mol Biol Transl Sci, 135, 203-225.
van der Velden, J., Merkus, D., Klarenbeek, B. R., James, A. T., Boontje, N. M., Dekkers, D. H., . . . Duncker, D. J. (2004). Alterations in myofilament function contribute to left ventricular dysfunction in pigs early after myocardial infarction. Circ Res, 95(11), e85-95. 
Verboven, K., & Vechetti, I. J. (2023). Editorial: Inter-organ crosstalk during exercise in health and disease: Extracellular vesicles as new kids on the block [Editorial]. Front Physiol, 14, 1180972.
Wasserman, D. H., & Ayala, J. E. (2005). Interaction of physiological mechanisms in control of muscle glucose uptake. Clin Exp Pharmacol Physiol, 32(4), 319-323.
Zolfaghari, R., Haghighi, A. H., Askari, R., & Hejazi, K. (2020). The Effect of Eight Weeks Aerobic Interval Exercise with Different Types of Volumes on Cardiovascular Risk Factors and Liver Enzymes in Women with Dyslipidemia.