Sarcopenic obesity: Myokines as potential diagnostic biomarkers and therapeutic targets?
Abstract
Sarcopenic obesity (SO) is a condition characterized by the occurrence of both sarcopenia and obesity and imposes a heavy burden on the health of the elderly. Controversies and challenges regarding the definition, diagnosis and treatment of SO still remain because of its complex pathogenesis and limitations. Over the past few decades, numerous studies have revealed that myokines secreted from skeletal muscle play significant roles in the regulation of muscle mass and function as well as metabolic homeostasis. Abnormalities in myokines may trigger and promote the pathogenesis underlying age-related and metabolic diseases, including obesity, sarcopenia, type 2 diabetes (T2D), and SO. This review mainly focuses on the role of myokines as potential biomarkers for the early diagnosis and therapeutic targets in SO.
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Numerous families of secreted signaling molecules bearing the suffix "-kines," such as myokines, osteokines, adipokines, and hepatokines, have been identified in more recent times.
“Hormones were identified and subsequently leveraged for use as therapeutics throughout the 20th century but it is only in more recent times that numerous families of secreted signaling molecules bearing the suffix “‐kines” such as myokines, 243 osteokines, adipokines, 244 and hepatokines 245 have been identified. 242”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [243]
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Alizadeh Pahlavani, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.811751 · Cited by 145 · see citing works
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BackgroundInfluentialSarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk
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BackgroundObesity phenotypes and cardiovascular risk: From pathophysiology to clinical management
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“In addition to myostatin, sarcopenia and sarcopenic obesity are associated with a dysregulation of other myokines with important cardiometabolic functions, such as IL-6, FNDC5/ irisin, fibroblast growth factor 21 or brain-derived neurotrophic factor, which play a critical role in skeletal muscle mass and function as w…”
BackgroundSearching for the link between inflammaging and sarcopenia
Wang, T. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101611 · Cited by 88 · see citing works
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Ageing of skeletal muscle extracellular matrix and mitochondria: finding a potential link
Cai, L., Shi, L., Peng, Z., Sun, Y., & Chen, J. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2240707 · Cited by 60 · see citing works
“It is highly expressed in skeletal muscle and plays a role in enhancing muscle hypertrophy in response to physical exercise [143].”
BackgroundMinniti, G., Pescinini-Salzedas, L. M., Minniti, G. A. D. S., Laurindo, L. F., Barbalho, S. M., Sinatora, R. V., Sloan, L. A., Haber, R. S. D. A., Araújo, A. C., Quesada, K. R., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113452 · Cited by 52 · see citing works
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Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions
Wang, T., Zhou, D., & Hong, Z. (2025) · MedComm · doi:10.1002/mco2.70030 · Cited by 46 · see citing works
Cytokines and exosomal miRNAs in skeletal muscle–adipose crosstalk
Guo, L., Quan, M., Pang, W., Yin, Y., & Li, F. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.07.006 · Cited by 48 · see citing works
Zamboni, M. M., Mazzali, G., Brunelli, A., Saatchi, T., Urbani, S., Giani, A., Rossi, A. P., Zoico, E., & Fantin, F. (2022) · Cells · doi:10.3390/cells11213361 · Cited by 42 · see citing works
“BDNF affects myogenesis through activation of satellite cells [71], especially in response to muscle injury; it has also been suggested as a regulator of neuromuscular function during the aging process, with possible implications in sarcopenia and SO [72].”
BackgroundLu, Z., Wang, Z., Zhang, X., & Ning, K. (2024) · Biomolecules · doi:10.3390/biom14101205 · Cited by 36 · see citing works
“…has been shown to be expressed in almost all tissues and organs of eukaryotes, with particularly high expression in skeletal muscle. for 8 weeks) bone in mice training (60 min/day, One study reported that the expression of FNDC5 was nearly 200-fold higher in muscle tissue than in adipocytes [79].”
BackgroundWong, C. J. K., Tai, Y. K., Yap, J. L. Y., Fong, C. H. H., Loo, L. S. W., Kukumberg, M., Fröhlich, J., Zhang, S., Li, J., Wang, J., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121658 · Cited by 35 · see citing works
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BackgroundKim, J., Shin, S., & Kwon, E. (2023) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202200729 · Cited by 36 · see citing works
Exploring exercise-driven exerkines: unraveling the regulation of metabolism and inflammation
Zhou, N., Gong, L., Zhang, E., & Wang, X. (2024) · PeerJ · doi:10.7717/peerj.17267 · Cited by 34 · see citing works
“It plays a role in regulating metabolic homeostasis, muscle growth, in fl ammation, and premature aging ( Guo, Li & Xiao, 2020 ).”
BackgroundJurdana, M., & Čemažar, M. (2024) · Radiology and Oncology · doi:10.2478/raon-2024-0011 · Cited by 27 · see citing works
“37-40 This results in a decrease in oxidative capacities, mitochondrial number, atrophy of fast type II muscle fibres and neurodegeneration, decrease in protein synthesis and increase muscle protein degradation.”
BackgroundTeixeira, L. A. D. C., Soares, L. A., da Fonseca, S. F., Gonçalves, G. T., dos Santos, J. M., Viegas, Â. A., Parentoni, A. N., Figueiredo, P. H. S., Mendonça, V. A., & Lacerda, A. C. R. (2024) · Scientific Reports · doi:10.1038/s41598-024-76417-7 · Cited by 25 · see citing works
“The pathophysiology of sarcopenic obesity involves the infiltration and storage of intra-and intermuscular fat, increased inflammation and muscle catabolism 10,34 .”
BackgroundCrucial Regulatory Role of Organokines in Relation to Metabolic Changes in Non-Diabetic Obesity
Lőrincz, H., Somodi, S., Ratku, B., Harangi, M., & Paragh, G. (2023) · Metabolites · doi:10.3390/metabo13020270 · Cited by 25 · see citing works
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FGF19 protects against obesity-induced bone loss by promoting osteogenic differentiation
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Self-citationBorba, V. Z. C., & Costa, T. M. D. R. L. (2024) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-4292-2024-0084 · Cited by 21 · see citing works
“Proinflammatory cytokines, such as interleukin (IL)-6, IL-1, and tumor necrosis factor-α (TNF-α ), play an important role in muscle homeostasis and can contribute to the pathogenesis of obesity, sarcopenia, and sarcopenic obesity by disrupting metabolic homeostasis (18).”
InfluentialResearch Progress on the Effect and Mechanism of Exercise Intervention on Sarcopenia Obesity
Chen, J., Jia, S., Guo, C., Fan, Z., Yan, W., & Dong, K. (2024) · Clinical Interventions in Aging · doi:10.2147/cia.s473083 · Cited by 21 · see citing works
“64 IGF-1 is a key regulator of muscle growth and regeneration.”
BackgroundUnderstanding the development of sarcopenic obesity
Gross, D. C., Cheever, C. R., & Batsis, J. A. (2023) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2023.2267672 · Cited by 19 · see citing works
“After exercise, levels of the inflammatory markers IL-6 and TNF-α decrease, and the level of insulin-like growth factor one (IGF-1) increases [105,106].”
BackgroundMakiel, K., Suder, A., Targosz, A., Maciejczyk, M., & Haim, A. (2023) · Biomolecules · doi:10.3390/biom13050852 · Cited by 18 · see citing works
“All authors have read and agreed to the published version of the manuscript.”
BackgroundKumari, M., & Khanna, A. (2022) · Annals of Geriatric Medicine and Research · doi:10.4235/agmr.22.0081 · Cited by 16 · see citing works
Inflammatory Biomarkers in Older Women with Obesity, Sarcopenia, and Sarcopenic Obesity
Teixeira, L. A. D. C., de Avelar, N. C. P., Parentoni, A. N., dos Santos, J. M., Leopoldino, A. A. O., Costa, S. P., Arrieiro, A. N., Soares, L. A., Nobre, J. N. P., Brant, F. P., et al. (2023) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2023.05.022 · Cited by 15 · see citing works
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Lim, G., Lee, H., & Lim, Y. (2022) · Biomedicines · doi:10.3390/biomedicines10102529 · Cited by 15 · see citing works
“Many studies have examined myokines as potential biomarkers that reflect whole-body metabolism homeostasis [28].”
BackgroundLosasso, M. R., Parussolo, M. L. C., Silva, A. O., Direito, R., Quesada, K. R., Detregiachi, C. R. P., Bechara, M. D., Méndez‐Sánchez, N., Abenavoli, L., Araújo, A. C., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104673 · Cited by 13 · see citing works
Sharma, A. R., Chatterjee, S., Lee, Y., & Lee, S. (2023) · Aging and Disease · doi:10.14336/ad.2023.00903 · Cited by 15 · see citing works
“Sarcopenia, Type 2 diabetes, and obesity are some metabolic diseases associated with age [76-78].”
BackgroundStudy on the comorbid mechanisms of sarcopenia and late-life depression
Wu, J., Tang, J., Huang, D., Wang, Y., Zhou, E., Ru, Q., Xu, G., Chen, L., & Wu, Y. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115538 · Cited by 12 · see citing works
“IL-6 has a dual role: it can promote muscle hypertrophy by regulating satellite cells[227] and activate anti-inflammatory pathways, including IL-10, to suppress TNF-α expression[228].”
LeDrew, M., Sadri, P., Peil, A., & Farahnak, Z. (2025) · Nutrients · doi:10.3390/nu17172758 · Cited by 12 · see citing works
“In summary, myostatin is recognized not only as a potential biomarker for muscle status but also as a promising therapeutic target for managing muscle degenerative diseases [10,18].”
InfluentialPossible Mechanisms Linking Obesity, Steroidogenesis, and Skeletal Muscle Dysfunction
Sheptulina, A. F., Antyukh, K. Y., Kiselev, A. R., Mitkovskaya, N. P., & Drapkina, O. M. (2023) · Life · doi:10.3390/life13061415 · Cited by 11 · see citing works
“Currently, they are extensively studied as potential prognostic markers and therapeutic targets [20,21].”
BackgroundImmune activation induced by dysregulated lipid metabolism in the pathogenesis of type 2 diabetes
Yang, H., Yu, W., Mao, Q., & Zhao, L. (2025) · World Journal of Diabetes · doi:10.4239/wjd.v16.i12.114395 · Cited by 11 · see citing works
Immunogenetic Aspects of Sarcopenic Obesity
Mazurkiewicz, Ł., Czernikiewicz, K., & Grygiel‐Górniak, B. (2024) · Genes · doi:10.3390/genes15020206 · Cited by 10 · see citing works
“Some of them (like IL-6) have anti-inflammatory activity in the physiological state, while they gain pro-inflammatory properties in the obesity state [10].”
BackgroundInfluentialSarcopenic obesity and brain health: A critical appraisal of the current evidence
Booranasuksakul, U., Guan, Z., Macdonald, I. A., Tsintzas, K., Stephan, B. C. M., & Siervo, M. (2025) · Nutrition Bulletin · doi:10.1111/nbu.12725 · Cited by 10 · see citing works
Kim, N. Y., & Choi, Y. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12113676 · Cited by 10 · see citing works
Rauen, M., Hao, D., Müller, A., Mückter, E., Bollheimer, L. C., & Nourbakhsh, M. (2021) · Biology · doi:10.3390/biology10121318 · Cited by 10 · see citing works
“The high level of systemic inflammatory proteins was suggested to play a key role in the development of human sarcopenic obesity; however, it has been difficult to clarify which proteins are clinically relevant [21,22,24].”
BackgroundFaiz, H., Heiston, E. M., & Malin, S. K. (2023) · Journal of Diabetes Research · doi:10.1155/2023/4618215 · Cited by 9 · see citing works
“BAIBA has been implicated as a potential target for lowering T2D risk [29].”
BackgroundMyokines and Biomarkers of Frailty in Older Inpatients with Undernutrition: A Prospective Study
Liu, H., Li, W., Zhu, M., Wen, X., Jin, J., Wang, H., Lv, D., Zhao, S., Wu, X., & Jiao, J. (2024) · The Journal of Frailty & Aging · doi:10.14283/jfa.2024.9 · Cited by 9 · see citing works
“From embryonic development to adulthood, MSTN negatively regulates mass, impairs muscle synthesis, and increases muscle catabolism (44-46).”
Lack of association between serum myonectin levels and sarcopenia in older Asian adults
Ji, S., Park, S. J., Lee, J. Y., Baek, J. Y., Jung, H., Kim, K., Yoo, H. J., Jang, I., & Kim, B. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112229 · Cited by 7 · see citing works
Mückter, E., Lozoya, M., Müller, A., Weissig, V., & Nourbakhsh, M. (2022) · Biology · doi:10.3390/biology11050701 · Cited by 7 · see citing works
Li, W., Hu, M., Yin, Q., Liu, Y., Chen, L., Ru, Q., Xu, G., & Wu, Y. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1616874 · Cited by 6 · see citing works
“Myostatin, also known as growth differentiation factor 8, is primarily expressed in skeletal muscle(Baczeketal.,2020)andactsasanegativeregulatorofmuscle mass and development (Guo et al., 2020).”
Hart, D. A., Zernicke, R. F., & Shrive, N. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179949 · Cited by 6 · see citing works
Lin, W. W., Su, H., Lan, X. Y., Ni, Q. Y., Wang, X. Y., Cui, K. Y., & Zhang, L. (2024) · Science & Sports · doi:10.1016/j.scispo.2023.09.002 · Cited by 5 · see citing works
Muthukrishnan, R., Alzaabi, A. M. M. A., Ismail, M., Kandakurthi, P. K., Durairaj, S., Sukumar, S., & Gopal, K. (2025) · Journal of Medicine and Life · doi:10.25122/jml-2024-0277 · Cited by 4 · see citing works
Qi, D. E. N. G., Huang, J., Wang, C., & Liang, J. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27062746 · Cited by 4 · see citing works
“Notably, independent centenarians exhibit significantly elevated serum IL-15 concentrations, implying a protective effect against aging-related debility [98].”
Laboratory markers of osteosarcopenic obesity
Гриценко, О. В., Gruzdeva, O. V., Chumakova, G. A., & Барбараш, О. Л. (2023) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2023-5563 · Cited by 4 · see citing works
Ai, Y., Xu, R., & Liu, L. (2021) · Research Square · doi:10.21203/rs.3.rs-717363/v1 · Cited by 4 · see citing works
Jiang, H., Zhang, Y., Luo, Z., Tang, X., 赫一佑, & Hao, G. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1808488 · Cited by 3 · see citing works
“Speci fi cally, IL-10, as a powerful anti-in fl ammatory cytokine, directly inhibits macrophage M1 polarization and the release of pro-in fl ammatory factors like TNF-a and IL-2, improving the pro-in fl ammatory microenvironment of muscle (137).”
Kim, J. J., Bressel, E., Kim, M., Kim, T., Koh, S.-H., & Kim, D. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14144981 · Cited by 2 · see citing works
“IL-15 is abundantly expressed in skeletal muscle and plays a key role in promoting muscle hypertrophy by increasing in response to exercise [9].”
Oropharyngeal cancer associated with sarcopenic obesity and sarcopenic weight loss
Manjusha, M., & Saravanan, M. (2022) · Oral Oncology · doi:10.1016/j.oraloncology.2022.106101 · Cited by 2 · see citing works
Habib, S. S., Bashir, S., & Habib, S. H. (2020) · Khyber Medical University Journal · doi:10.35845/kmuj.2020.20254 · Cited by 2 · see citing works
Underlying mechanisms of sarcopenic obesity
Rauen, M., Bollheimer, L. C., & Nourbakhsh, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822146-4.00005-3 · Cited by 2 · see citing works
Obesity, Myokines, and Metabolic Health
Malandrino, N., & Ahima, R. S. (2023) · Springer eBooks · doi:10.1007/978-3-031-40116-9_56 · Cited by 2 · see citing works
Song, G. Y. (2025) · Korean Journal of Geriatrics & Gerontology · doi:10.15656/kjgg.2025.26.1.9 · Cited by 1 · see citing works
Tata, R. K., Rao, A. R., Poonia, Y., Chatterjee, P., Mehta, P. K., & Chakrawarty, A. (2026) · BMC Geriatrics · doi:10.1186/s12877-026-07098-2 · Cited by 2 · see citing works
“These were not assessed in our study and warrant further investigation in larger prospective cohorts [38].”
Jouzi, Z., & Omidi, M. (2023) · Modern Care Journal · doi:10.5812/mcj-142039 · Cited by 1 · see citing works
Teixeira, L. A. D. C., Soares, L. A., Costa, H. S., Nobre, J. N. P., Viegas, Â. A., de Avelar, N. C. P., Figueiredo, P. H. S., Parentoni, A. N., Mendonça, V. A., & Lacerda, A. C. R. (2025) · Scientific Reports · doi:10.1038/s41598-025-95368-1 · Cited by 1 · see citing works
“…encourage studies with biomarkers 3,40–42 , and advances in research point to possible diagnostic markers 3,32,41–43 , diagnostic accuracy studies with inflammatory mediators are relatively recent and scarce, and a marker with an established cutoff point has not been found either 6,10,11,22,44 .”
Obesity, Myokines, and Metabolic Health
Malandrino, N., & Ahima, R. S. (2023) · Springer eBooks · doi:10.1007/978-3-319-12125-3_56-1
Kukes, V. G., Furalyov, V. A., Амырхановна, Г. А., Parfenova, O. K., Grishin, D. V., & Sidorov, N. G. (2023) · Current Bioactive Compounds · doi:10.2174/0115734072273072231017104102
Kim, C.-Y., & Byun, Y.-H. (2025) · Exercise Science · doi:10.15857/ksep.2025.00108
ENDOCRINE FUNCTION OF SKELETAL MUSCLES
Vadzyuk, S. N., & Tabas, P. S. (2025) · Fìzìologìčnij žurnal · doi:10.15407/fz71.03.120
Du, X., Chenhang, Y., Huang, R., Zeng, Y., & Mao, S. (2025) · Journal of Science in Sport and Exercise · doi:10.1007/s42978-026-00375-x
Circulating cytokine profile in patients with obesity depending on the sarcopenia presence
Мамутовна, М. Э., Sheptulina, A. F., Valeeva, D. L., Yafarova, A. A., Timofeev, J. S., Metelskaya, V. A., & Drapkina, O. M. (2025) · Russian Journal of Preventive Medicine · doi:10.17116/profmed20252811166
Ai, Y., Xu, R., & Liu, L. (2021) · Figshare · doi:10.6084/m9.figshare.16570255
Ai, Y., Xu, R., & Liu, L. (2021) · Figshare · doi:10.6084/m9.figshare.16570258
Ai, Y., Xu, R., & Liu, L. (2021) · Figshare · doi:10.6084/m9.figshare.16570252
Sarcopenic Obesity and Hormones: A Narrative Review
Yu, D., & Zhou, B. (2025) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2025.1312003
Kopylov, A. E., Агарков, Н. М., & Abramov, A. A. (2025) · Russian Annals of Ophthalmology · doi:10.17116/oftalma202514106122
Xu, Y., 石龙凯, Chen, L., Liu, J., & Ding, W. (2025) · Scientific Reports · doi:10.1038/s41598-025-28449-w
“Studies have shown that exercise can upregulate anti-inflammatory cytokines such as IL-10, thereby counteracting the inhibitory effect of TNF-α on muscle protein synthesis and alleviating inflammation and oxidative stress in skeletal muscle 32,33 .”
Interleukin profile of patients with cataracts and sarcopenic obesity
Агарков, Н. М., Kopylov, A. E., Yablokov, M. M., & Абрамов, А. А. (2026) · Russian Ophthalmological Journal · doi:10.21516/2072-0076-2026-19-1-142-147
Yu, Y., He, Y., Wang, Y., Wu, C., Zhou, R., Chen, F., & Ma, W. (2026) · The FASEB Journal · doi:10.1096/fj.202601360r
“IL-10 deficiency leads to constitutive NF-κB activation, increased IL-6 production, and compromised muscle strength [162, 172, 173].”
Jiang, N., Wang, S., Zhang, J., & Jia, D.-D. (2026) · Cells · doi:10.3390/cells15110981
“…against age-related metabolic diseases by improving mitochondrial dysfunction [11,12], Physiological muscle hypertrophy resulting from chronic exercise training is critically associated with a panel of skeletal muscle-secreted factors, including myokines, growth factors, and myostatin [13–16].”
Mahmood, S., Safiyah, Fatima, M., Salman, M., & Siddiqui, B. (2026) · Bangladesh Journal of Endocrinology and Metabolism · doi:10.4103/bjem.bjem_15_26
- Authors
- Guo, A., Li, K., & Xiao, Q.
- Affiliations
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Corresponding author
- Xiao, Qian
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 139
- Pages
- 111022
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W3043914821
- Cited by
- 83
- References
- 286
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 9 · 2023: 20 · 2022: 16 · 2021: 12 · 2020: 1
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chongqing Medical University
- Topics
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- sarcopenic obesity, myokines, skeletal muscle, biomarkers, therapeutic target, sarcopenia, obesity, type 2 diabetes, aging, metabolic homeostasis, muscle mass and function
- MeSH terms
- Aged, Diabetes Mellitus, Type 2, Humans, Obesity, Biomarkers, Muscle, Skeletal, Sarcopenia
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