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Cited by 269Adipokines, Inflammation, and Metabolic DiseasesCytokine Signaling Pathways and InteractionsExercise and Physiological Responses

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

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Weigert, Cora, Brodbeck, Katrin, Staiger, Harald, Kausch, Christiana, Machicao, Fausto, Häring, Hans U., Schleicher, Erwin D.·2004·Journal of Biological Chemistry
DOI 10.1074/jbc.m312692200
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Abstract

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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Research works printed but not linked: 3

  1. Mohamed-Ali, 1997, J. Clin. Endocrinol. Metab., 82, 4196
  2. Libermann, 1990, Mol. Cell. Biol., 10, 2327
  3. 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.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-06
Volume
279
Issue
23
Pages
23942-23952
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m312692200
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
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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