The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
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]
In the citing paper
“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]
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TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
The anti-inflammatory effect of exercise
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Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
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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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