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Skeletal muscle inflammation and insulin resistance in obesity
Open accessAbstract
Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance.
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“The IKK/NF-kB pathway is activated by TNF-α, IL-1β, and free-fatty acids [62].”
From Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences (2020) · cites this paper as [62]
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van der Kolk, B. W., Saari, S., Lovrić, A., Arif, M., Alvarez, M., Ko, A., Miao, Z., Sahebekhtiari, N., Muniandy, M., Heinonen, S., et al. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100226 · Cited by 72
“Our findings related to concomitantly downregulated mitochondrial metabolism and upregulated inflammation in both tissues is intriguing and in line with previous findings in adipose tissue and skeletal muscle.(42) However, the underlyingmechanisms for the two seemingly closely connected biological phenomena remain unc…”
ResultCurrent and Future Nutritional Strategies to Modulate Inflammatory Dynamics in Metabolic Disorders
van den Brink, W., van Bilsen, J. H. M., Salic, K., Hoevenaars, F. P. M., Verschuren, L., Kleemann, R., Bouwman, J., Ronnett, G. V., van Ommen, B., & Wopereis, S. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00129 · Cited by 74
“The release of cytokines and myokines, in turn, contributes to insulin resistance and low-grade inflammation (37).”
BackgroundIglesias, P. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134490 · Cited by 79
“This defect is compounded by alterations in intracellular signaling (PI3K/Akt/mTOR), mitochondrial dysfunction and intramyocellular lipid accumulation, which interfere with insulin action through the activation of serine kinases [62].”
Huang, S., Ma, S.-Y., Ning, M., Yang, W., Ye, Y., Zhang, L., Shen, J., & Leng, Y. (2019) · Metabolism · doi:10.1016/j.metabol.2019.07.003 · Cited by 64
Gut microbiota and its metabolites: Bridge of dietary nutrients and obesity-related diseases
Zhou, M., Johnston, L. J., Wu, C., & Ma, X. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1986466 · Cited by 67
Higher Risk of Sarcopenia in Older Adults with Type 2 Diabetes: NHANES 1999–2018
Dai, S., Shu, D., Meng, F., Chen, Y., Wang, J., Liu, X., Xiao, X., Guo, W., & Chen, F. (2023) · Obesity Facts · doi:10.1159/000530241 · Cited by 63
The Impact of Immune Cells on the Skeletal Muscle Microenvironment During Cancer Cachexia
VanderVeen, B. N., Murphy, E. A., & Carson, J. A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.01037 · Cited by 61
“While monocytes and MCP-1 stimulate the release of VEGF by endothelial cells to increase myofibrillar vascularization during the later stages of repair (Hong et al., 2005), tumor associated macrophages (TAMs) promote the release of VEGF to promote tumor vascularization (Wynn et al., 2013).”
BackgroundSkeletal muscle and MASLD: Mechanistic and clinical insights
Marjot, T., Armstrong, M. J., & Stine, J. G. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000711 · Cited by 76
“[29,30] For example, in both obesity and during stimulation with inflammatory molecules, myocytes upre-gulate chemokine secretion (eg, MCP-1), which induces immune cell migration in parallel with accumulating insulin resistance.”
Shabir, K., Brown, J. E. P., Afzal, I., Gharanei, S., Weickert, M. O., Barber, T. M., Kyrou, I., & Randeva, H. S. (2021) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2021.05.002 · Cited by 63
“in skeletal muscle and adipose tissue) obesity-related inflammation can impact on insulin signalling, leading to insulin resistance [27].”
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“Furthermore, a previous study indicated that immune cells can also cause myocyte inflammation by secreting pro-inflammatory molecules for adverse regulatory effects on myocyte metabolism [54].”
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
Obesity-Related Heart Failure with Preserved Ejection Fraction
Harada, T., & Obokata, M. (2020) · Heart Failure Clinics · doi:10.1016/j.hfc.2020.02.004 · Cited by 60
Inflammation and Metabolic Complications in HIV
Bourgi, K., Wanjalla, C. N., & Koethe, J. R. (2018) · Current HIV/AIDS Reports · doi:10.1007/s11904-018-0411-2 · Cited by 56
Hartogh, D. J. D., Vlavcheski, F., Giacca, A., & Tsiani, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144900 · Cited by 60
“Elevated inflammation levels were correlated with the development of muscle insulin resistance [57].”
BackgroundJorquera, G., Russell‐Guzmán, J., Monsalves‐Álvarez, M., Cruz, G., Valladares-Ide, D., Basualto-Alarcón, C., Barrientos, G. C., Estrada, M., & Llanos, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063254 · Cited by 61
“Interestingly, a crucial role of inflammatory cytokines has been proposed to mediate abnormal IRS-1 phosphorylation and other effects on the insulin signaling cascade [1,2] (Figure 1).”
BackgroundT Cells in Adipose Tissue in Aging
Antony, A. K., Lian, Z., & Wu, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02945 · Cited by 57
“In addition to their crucial role in visceral adipose inflammation, T cells, conventional CD4+ and CD8+ T cells in particular, also infiltrate into skeletal muscle, mainly localized within intermyocellular and perimuscular adipose tissue, and play substantial roles in skeletal muscle inflammation in obesity (59, 64, 6…”
BackgroundSelf-citationChen, X., Li, H., Wang, K., Liang, X., Wang, W., Hu, X., Huang, Z., & Wang, Y. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01286 · Cited by 58
“As we known, there has established a link between chronic inflammation and obesityassociated complications (Lumeng and Saltiel, 2011; Wu and Ballantyne, 2017).”
BackgroundKobayashi, M., Yoshino, O., Nakashima, A., Ito, M., Nishio, K., Ono, Y., Kusabiraki, T., Kunitomi, C., Takahashi, N., Harada, M., et al. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110792 · Cited by 56
“FFA also plays an important role in insulin resistance (33).”
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Apostolopoulou, M., Mastrototaro, L., Hartwig, S., Pesta, D. H., Straßburger, K., Filippo, E. D., Jeleník, T., Karusheva, Y., Gancheva, S., Markgraf, D. F., et al. (2021) · Science Advances · doi:10.1126/sciadv.abi9551 · Cited by 54
“SGPT (U/liter) 41 (29, 62)&& 33 (25, 61) 29 (20, 37) 27 (19, 32) 24 (21, 29) 24 (20, 29)”
BackgroundYustisia, I., Tandiari, D., Cangara, M. H., Hamid, F., & Daud, N. A. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e10896 · Cited by 63
NAD+ metabolism-based immunoregulation and therapeutic potential
Fang, J., Chen, W., Hou, P., Liu, Z., Zuo, M., Liu, S., Feng, C., Han, Y., Li, P., Shi, Y., et al. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01031-5 · Cited by 55
Qu, J., Tan, S., Xie, X., Wu, W., Zhu, H., Li, H., Liao, X., Wang, J., Zhou, Z.-A., Huang, S. M., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.659626 · Cited by 53
“Further, obesity and IR are closely related to inflammation of metabolic tissues, including the liver, muscle, and adipose tissue (Winer et al., 2016; Wu and Ballantyne, 2017; Ghorpade et al., 2018).”
HDAC11, an emerging therapeutic target for metabolic disorders
Chen, H., Xie, C., Chen, Q., & Zhuang, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.989305 · Cited by 55
Liu, B., Hutchison, A. T., Thompson, C. H., Lange, K. M., & Heilbronn, L. K. (2019) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2019.07.001 · Cited by 54
Immunometabolism and metainflammation in obesity
Romantsova, T. I., & Sych, Y. P. (2019) · Obesity and metabolism · doi:10.14341/omet12218 · Cited by 63
Metadata
- Authors
- Wu, H., & Ballantyne, C. M.
- Affiliations
- Houston Methodist (US)
- Corresponding author
- Ballantyne, Christie M.
- Venue
- Journal of Clinical Investigation
- Published
- 2017-01-03
- Volume
- 127
- Issue
- 1
- Pages
- 43-54
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5199705
- OpenAlex
- W2561422649
- Cited by
- 695
- References
- 171
- Citations by year
- 2026: 66 · 2025: 92 · 2024: 103 · 2023: 84 · 2022: 98 · 2021: 95 · 2020: 76 · 2019: 45 · 2018: 29 · 2017: 7
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (AHA16GRNT30410012)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL098839)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078847)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- skeletal muscle inflammation, insulin resistance, obesity, type 2 diabetes, chronic inflammation, immune cell infiltration, proinflammatory molecules, paracrine signaling, visceral adipose tissue, glucose homeostasis
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Glucose, Humans, Inflammation, Insulin Resistance, Myositis, Obesity, Muscle, Skeletal, Muscle Fibers, Skeletal, Intra-Abdominal Fat
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