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Palmitate, but Not Unsaturated Fatty Acids, Induces the Expression of Interleukin-6 in Human Myotubes through Proteasome-dependent Activation of Nuclear Factor-κB
Open accessAbstract
Circulating interleukin-6 (IL-6), insulin, and free fatty acid (FFA) concentrations are associated with impaired insulin action in obese and type 2 diabetic individuals. However, a causal relationship between elevated plasma FFAs and IL-6 has not been shown. Because skeletal muscle represents a major target of impaired insulin action, we studied whether FFAs may affect IL-6 expression in human myotubes. We demonstrate that specifically saturated FFAs, e.g. palmitate (0.25 mm), induce IL-6 mRNA expression and protein secretion by a proteasome-dependent mechanism that leads to a rapid and chronic activation of nuclear factor-kappaB. Insulin, high glucose concentrations, or unsaturated FFAs did not activate IL-6 expression. In fact, the unsaturated FFA linoleate inhibited palmitate-induced IL-6 production. Because inhibition of palmitate metabolism by the acyl-CoA synthetase inhibitor triacsin C did not abolish IL-6 expression, it appears that the palmitate molecule per se exerts the observed effects. Furthermore, we show that in human myotubes, IL-6 activates the phosphorylation of signal transducer and activator of transcription 3 in concentrations similar to hepatocytes. However, no inhibitory effect of IL-6 on insulin action, determined as phosphatidylinositol 3-kinase association with insulin receptor substrate-1, Akt phosphorylation, and glycogen synthesis, was detected. We conclude that IL-6 expression may be modulated by the composition of circulating FFA, e.g. by diet, and that skeletal muscle cells could be target cells for IL-6.
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“Consumption of a soya isoflavone-enriched cereal bar (50 mg/d) for 8 weeks by postmenopausal women had no effect on CRP or other plasma markers of inflammation (813) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [813]
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“The actions of these stimuli serve to not only further induce tissue expression and secretion of IL-6 and TNFα (via the NFκB pathway, [3, 4]), but impair control of numerous signalling pathways regulating skeletal muscle insulin signalling, glucose uptake, mitochondrial fuel oxidation and respiration that impact negatively upon skeletal muscle energy homeostasis [2, 5–7].”
From Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading (2019) · cites this paper as [4]
Citations
Cites
1 retracted
Immunohistochemical detection of interleukin‐6 in human skeletal muscle fibers following exercise
Penkowa, M., Keller, C., Keller, P., Jauffred, S., & Pedersen, B. K. (2003) · The FASEB Journal · doi:10.1096/fj.03-0311fje · Cited by 157
RetractedNF-κB AND REL PROTEINS: Evolutionarily Conserved Mediators of Immune Responses
Ghosh, S., May, M. J., & Kopp, E. B. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.225 · Cited by 5,182
C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus
Pradhan, A. D. (2001) · JAMA · doi:10.1001/jama.286.3.327 · Cited by 4,433
Schreck, R., RIEBER, P., & Baeuerle, P. A. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07761.x · Cited by 3,793
Principles of interleukin (IL)-6-type cytokine signalling and its regulation
HEINRICH, P. C., BEHRMANN, I., HAAN, S., HERMANNS, H. M., MÜLLER-NEWEN, G., & SCHAPER, F. (2003) · Biochemical Journal · doi:10.1042/bj20030407 · Cited by 3,272
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
Listenberger, L. L., Han, X., Lewis, S. E., Cases, S., Farese, R. V., Ory, D. S., & Schaffer, J. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0630588100 · Cited by 2,075
Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-α,in Vivo1
Mohamed‐Ali, V., Goodrick, S., Rawesh, A., Katz, D. R., Miles, J. M., Yudkin, J. S., Klein, S., & Coppack, S. W. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4450 · Cited by 2,032
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884
Kern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e745 · Cited by 1,883
Yu, C., Chen, Y., Cline, G. W., Zhang, D., Zong, H., Wang, Y., Bergeron, R., Kim, J. K., Cushman, S. W., Cooney, G. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200958200 · Cited by 1,561
Flagged first, then by citations
Research works printed but not linked: 3
- Mohamed-Ali, 1997, J. Clin. Endocrinol. Metab., 82, 4196
- Libermann, 1990, Mol. Cell. Biol., 10, 2327
- Karin, 2000, Annu. Rev. Immunol., 16, 225
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Metadata
- Authors
- Weigert, C., Brodbeck, K., Staiger, H., Kausch, C., Machicao, F., Häring, H. U., & Schleicher, E. D.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Schleicher, Erwin D.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 279
- Issue
- 23
- Pages
- 23942-23952
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2028068170
- Cited by
- 269
- References
- 51
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 13 · 2016: 11 · 2015: 11 · 2014: 19 · 2013: 24 · 2012: 19
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- palmitate, interleukin-6, free fatty acids, saturated fatty acids, unsaturated fatty acids, linoleate, nuclear factor-kappaB, proteasome, myotubes, skeletal muscle, insulin resistance, type 2 diabetes, obesity, STAT3 phosphorylation, insulin signaling, acyl-CoA synthetase, triacsin C, IRS-1, Akt, glycogen synthesis
- MeSH terms
- NF-KappaB Inhibitor alpha, Acyl Coenzyme A, Cell Nucleus, Cells, Cultured, Cysteine Endopeptidases, DNA-Binding Proteins, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Fatty Acids, Nonesterified, Fatty Acids, Unsaturated, Gene Expression Regulation, Glucose, Glycogen, Humans, Insulin, Multienzyme Complexes, Phosphoproteins, Phosphorylation, Proto-Oncogene Proteins, RNA, Messenger, Time Factors, Blotting, Western, Signal Transduction, Trans-Activators, Interleukin-6, NF-kappa B, Protein Serine-Threonine Kinases, Muscle, Skeletal, Palmitic Acid, Linoleic Acid, Phosphatidylinositol 3-Kinases, Reverse Transcriptase Polymerase Chain Reaction, I-kappa B Proteins, Hepatocytes, Muscle Cells, Proteasome Endopeptidase Complex, STAT3 Transcription Factor, Proto-Oncogene Proteins c-akt, Insulin Receptor Substrate Proteins
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