Adipose–Muscle Crosstalk in Age-Related Metabolic Disorders: The Emerging Roles of Adipo-Myokines
Abstract
Obesity and type 2 diabetes account for a considerable proportion of the global burden of age-related metabolic diseases. In age-related metabolic diseases, tissue crosstalk and metabolic regulation have been primarily linked to endocrine processes. Skeletal muscle and adipose tissue are endocrine organs that release myokines and adipokines into the bloodstream, respectively. These cytokines regulate metabolic responses in a variety of tissues, including skeletal muscle and adipose tissue. However, the intricate mechanisms underlying adipose-muscle crosstalk in age-related metabolic diseases are not fully understood. Recent exciting evidence suggests that myokines act to control adipose tissue functions, including lipolysis, browning, and inflammation, whereas adipokines mediate the beneficial actions of adipose tissue in the muscle, such as glucose uptake and metabolism. In this review, we assess the mechanisms of adipose-muscle crosstalk in age-related disorders and propose that the adipokines adiponectin and spexin, as well as the myokines irisin and interleukin-6 (IL-6), are crucial for maintaining the body's metabolic balance in age-related metabolic disorders. In addition, these changes of adipose-muscle crosstalk in response to exercise or dietary flavonoid consumption are part of the mechanisms of both functions in the remission of age-related metabolic disorders. A better understanding of the intricate relationships between adipose tissue and skeletal muscle could lead to more potent therapeutic approaches to prolong life and prevent age-related metabolic diseases.
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Adiponectin is released from the AT and plays a key role in regulating metabolic functioning of the SM, including enhanced mitochondrial function, Glucose Transporter 4 (GLUT4) translocation (to improve glucose uptake), and fatty acid oxidation.
“Adiponectin is released from the AT and plays a key role in regulating metabolic functioning of the SM, including enhanced mitochondrial function, Glucose Transporter 4 (GLUT4) translocation (to improve glucose uptake), and fatty acid oxidation [56].”
From Optimised Skeletal Muscle Mass as a Key Strategy for Obesity Management (2025) · cites this paper as [56]
Disruption in signaling pathways of adipokines and myokines contributes to the pathogenesis of sarcopenic obesity, described as a convergence of high fat mass and declining muscle function with aging.
“Disruption in these signaling pathways contributes to the pathogenesis of sarcopenic obesity, which Fang et al. describe as a convergence of high fat mass and declining muscle function with aging”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [92]
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Irisin has no effect on lipolysis in 3T3-L1 adipocytes or fatty acid metabolism in HepG2 hepatocytes
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Serum levels of nesfatin-1 and irisin in obese children
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Development of metabolic dysfunction in mice lacking chemerin
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Self-citationEmerging central and peripheral actions of spexin in feeding behavior, leptin resistance and obesity
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Self-citationRegular Swimming Exercise Attenuated Neuroma Pain in Rats: Involvement of Leptin and Adiponectin
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Serum Spexin is Correlated with Lipoprotein(a) and Androgens in Female Adolescents
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Self-citationExercise training rescues adipose tissue spexin expression and secretion in diet-induced obese mice
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Mutation of spexin2 promotes feeding, somatic growth, adiposity, and insulin resistance in zebrafish
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Glucagon-like peptide-1 receptor agonists and muscle mass effects
Ceasovschih, A., Asaftei, A., Lupo, M. G., Kotlyarov, S., Bartušková, H., Balta, A., Sorodoc, V., Sorodoc, L., & Banach, M. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107927 · Cited by 64 · see citing works
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“Disruption in these signaling pathways contributes to the pathogenesis of sarcopenic obesity, which Fang et al. describe as a convergence of high fat mass and declining muscle function with aging [92].”
Optimised Skeletal Muscle Mass as a Key Strategy for Obesity Management
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“In addition to the aging-related decline in SM mass and function, there are other obesity-related factors that can diminish SM mass through the effects of adipokines and cytokines outlined in the last section.”
InfluentialHerouvi, D., Vlachopapadopoulou, E. A., Vakaki, M., Gouriotis, D., Marmarinos, A., Kalpia, C., Kossiva, L., Tsolia, M., & Karavanaki, K. (2024) · Endocrine · doi:10.1007/s12020-024-04139-x · Cited by 5 · see citing works
- Authors
- Fang, P., She, Y., Yu, M., Min, W., Shang, W., & Zhang, Z.
- Affiliations
- Nanjing University of Chinese Medicine (CN)
- Yangzhou University (CN)
- Corresponding author
- Fang, Penghua
- Shang, Wenbin
- Zhang, Zhenwen
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2023-02
- Volume
- 84
- Pages
- 101829
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W4312085090
- Cited by
- 62
- References
- 201
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 16 · 2023: 8
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Administration of Traditional Chinese Medicine of Jilin Province (YB2020087)
- National Natural Science Foundation of China (81803792)
- Nanjing University of Chinese Medicine (NZY81803792)
- Priority Academic Program Development of Jiangsu Higher Education Institutions (ZYX03KF058)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- myokines, adipokines, adiponectin, spexin, irisin, interleukin-6, obesity, type 2 diabetes, skeletal muscle glucose uptake, insulin sensitivity, lipolysis, brown adipose tissue browning, inflammation, physical activity, dietary flavonoids, aging
- MeSH terms
- Adipose Tissue, Diabetes Mellitus, Type 2, Humans, Obesity, Muscle, Skeletal, Adipokines
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