Cited by 59NF-κB Signaling PathwaysAdipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and Cancer

Lipid induced overexpression of NF-κB in skeletal muscle cells is linked to insulin resistance

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Barma, Pomy, Bhattacharya, Sushmita, Bhattacharya, Anirban, Kundu, Rakesh, Dasgupta, Suman, Biswas, Anindita, Bhattacharya, Shelley, Roy, Sib Sankar +1 more·2009·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Abstract

Lipid induced NF-kappaB activation is known to be associated with insulin resistance and type2 diabetes. Here we show that incubation of L6 skeletal muscle cells with palmitate significantly increased NF-kappaB p65 and NF-kappaB p50 expression along with their phosphorylation. NF-kappaB p65 siRNA inhibited palmitate induced overexpression of NF-kappaB p65 indicating palmitate effect on transcriptional activation. RT-PCR and real time PCR experiments also showed a significant increase in NF-kappaB p65 gene expression due to palmitate. Overexpression of NF-kappaB p65 by palmitate was linked to impairment of insulin activity. Palmitate effect on NF-kappaB gene and protein expression was found to be mediated by phospho-PKCepsilon as calphostin C (an inhibitor of PKC) and epsilonV1 (PKCepsilon translocation inhibitor) significantly reduced NF-kappaB expression. To understand the underlying mechanism, we purified NF-kappaB and pPKCepsilon from palmitate incubated skeletal muscle cells and their interaction in cell free system demonstrated the transfer of phosphate from PKCepsilon to NF-kappaB. This prompted us to transduct pPKCepsilon to the skeletal muscle cells. These cells showed increased amount of pNF-kappaB and NF-kappaB. Excess of NF-kappaB p65 pool thus created in the cells made them insulin resistant. Addition of NF-kappaB p65 siRNA and SN50 inhibited palmitate induced NF-kappaB p65 expression indicating NF-kappaB regulation of its gene expression. Increase of NF-kappaB did not affect the activation of IKK/IkappaB indicating NF-kappaB p65 expression to be a distinct effect of palmitate. Since NF-kappaB p65 is linked to several diseases, including type2 diabetes, this report may be important in understanding the pathogenicity of these diseases.

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Crossref · 10.1016/j.bbadis.2008.11.014

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  • The actions of proinflammatory stimuli impair control of numerous signalling pathways regulating skeletal muscle insulin signalling, glucose uptake, mitochondrial fuel oxidation and respiration, impacting negatively upon skeletal muscle energy homeostasis.

    “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].”

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Authors
Barma, P., Bhattacharya, S., Bhattacharya, A., Kundu, R., Dasgupta, S., Biswas, A., Bhattacharya, S., Roy, S. S., & Bhattacharya, S.
Affiliations
  • Indian Institute of Chemical Biology (IN)
  • Visva-Bharati University (IN)
Corresponding author
Bhattacharya, Samir
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2009-03
Volume
1792
Issue
3
Pages
190-200
ISSN
0925-4439 (ISSN-L)
OpenAlex
W2129962371
Cited by
59
References
60
Citations by year
2026: 3 · 2025: 2 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 6 · 2014: 2 · 2013: 5 · 2012: 6
FWCI
1.48
Type
journal article
Language
en
Open access
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
  • Council of Scientific and Industrial Research, India
  • University Grants Commission
  • University of Illinois at Urbana-Champaign
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
NF-κB p65, palmitate, insulin resistance, skeletal muscle cells, protein kinase C epsilon, calphostin C, NF-κB phosphorylation, type 2 diabetes, SN50, siRNA knockdown
MeSH terms
Animals, Cell Line, Diabetes Mellitus, Type 2, Insulin Resistance, Palmitates, Phosphorylation, Muscle, Skeletal, RNA, Small Interfering, Lipid Metabolism, Rats, Protein Kinase C-epsilon, Transcription Factor RelA, NF-kappa B p50 Subunit

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