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

Palmitate, but Not Unsaturated Fatty Acids, Induces the Expression of Interleukin-6 in Human Myotubes through Proteasome-dependent Activation of Nuclear Factor-κB

Open access
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
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1074/jbc.m312692200

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Consumption of a soya isoflavone-enriched cereal bar at 50 mg per day for eight weeks by postmenopausal women had no effect on CRP or other plasma markers of inflammation.

    “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]

  • The actions of proinflammatory stimuli further induce tissue expression and secretion of IL-6 and TNFα via the NFκB pathway.

    “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]

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Related

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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Rehabilitation › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review