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Lipid Induced Overexpression of NF-κB in Skeletal Muscle Cells is Linked to Insulin Resistance

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Title Lipid Induced Overexpression of NF-κB in Skeletal Muscle Cells is Linked to Insulin Resistance
 
Creator Barma, Pomy
Bhattacharya, Sushmita
Bhattacharya, Anirban
Kundu, Rakesh
Dasgupta, Suman
Biswas, Anindita
Bhattacharya, Shelley
Roy, Sib Sankar
Bhattacharya, Samir
 
Subject Cell Biology & Physiology
 
Description Lipid induced NF-κB 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-κB p65 and NF-κB
p50 expression along with their phosphorylation. NF-κB p65 siRNA inhibited palmitate induced overexpression
of NF-κB p65 indicating palmitate effect on transcriptional activation. RT-PCR and real time PCR
experiments also showed a significant increase in NF-κB p65 gene expression due to palmitate.
Overexpression of NF-κB p65 by palmitate was linked to impairment of insulin activity. Palmitate effect on
NF-κB gene and protein expression was found to be mediated by phospho-PKCɛ as calphostin C (an inhibitor
of PKC) and ɛV1 (PKCɛ translocation inhibitor) significantly reduced NF-κB expression. To understand the
underlying mechanism, we purified NF-κB and pPKCɛ from palmitate incubated skeletal muscle cells and
their interaction in cell free system demonstrated the transfer of phosphate from PKCɛ to NF-κB. This
prompted us to transduct pPKCɛ to the skeletal muscle cells. These cells showed increased amount of pNF-κB
and NF-κB. Excess of NF-κB p65 pool thus created in the cells made them insulin resistant. Addition of NF-κB
p65 siRNA and SN50 inhibited palmitate induced NF-κB p65 expression indicating NF-κB regulation of its
gene expression. Increase of NF-κB did not affect the activation of IKK/IκB indicating NF-κB p65 expression to
be a distinct effect of palmitate. Since NF-κB p65 is linked to several diseases, including type2 diabetes, this
report may be important in understanding the pathogenicity of these diseases.
 
Publisher Elsevier
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1357/1/BIOCHIMICA_ET_BIOPHYSICA_ACTA%2DMOLECULAR_BASIS_OF_DISEASE___1792(_3)_190%2D200;2009[96].pdf
Barma, Pomy and Bhattacharya, Sushmita and Bhattacharya, Anirban and Kundu, Rakesh and Dasgupta, Suman and Biswas, Anindita and Bhattacharya, Shelley and Roy, Sib Sankar and Bhattacharya, Samir (2009) Lipid Induced Overexpression of NF-κB in Skeletal Muscle Cells is Linked to Insulin Resistance. BBA - Biochimica et Biophysica Acta, 1792 (3). pp. 190-200.
 
Relation http://dx.doi.org/10.1016/j.bbadis.2008.11.014
http://www.eprints.iicb.res.in/1357/