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Amelioration of Mitochondrial Dysfunction-Induced Insulin Resistance in Differentiated 3T3-L1 Adipocytes via Inhibition of NF-κB Pathways

1
Department of Bioprocess Engineering, Faculty of Chemical Engineering, University Teknologi Malaysia, Skudai 81310, Malaysia
2
Institute of Bioproduct Development, University Teknologi Malaysia, Skudai 81310, Malaysia
3
Innovation Centre in Agritechnology for Advanced Bioprocessing (ICA), University Teknologi Malaysia, Skudai 81310, Malaysia
4
Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
5
Clinical Investigation Centre, 13th Floor Main Tower, University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(12), 22227-22257; https://doi.org/10.3390/ijms151222227
Received: 13 September 2014 / Revised: 14 November 2014 / Accepted: 15 November 2014 / Published: 2 December 2014
(This article belongs to the Section Biochemistry)
A growing body of evidence suggests that activation of nuclear factor kappa B (NF-κB) signaling pathways is among the inflammatory mechanism involved in the development of insulin resistance and chronic low-grade inflammation in adipose tissues derived from obese animal and human subjects. Nevertheless, little is known about the roles of NF-κB pathways in regulating mitochondrial function of the adipose tissues. In the present study, we sought to investigate the direct effects of celastrol (potent NF-κB inhibitor) upon mitochondrial dysfunction-induced insulin resistance in 3T3-L1 adipocytes. Celastrol ameliorates mitochondrial dysfunction by altering mitochondrial fusion and fission in adipocytes. The levels of oxidative DNA damage, protein carbonylation and lipid peroxidation were down-regulated. Further, the morphology and quantification of intracellular lipid droplets revealed the decrease of intracellular lipid accumulation with reduced lipolysis. Moreover, massive production of the pro-inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were markedly depleted. Insulin-stimulated glucose uptake activity was restored with the enhancement of insulin signaling pathways. This study signified that the treatments modulated towards knockdown of NF-κB transcription factor may counteract these metabolic insults exacerbated in our model of synergy between mitochondrial dysfunction and inflammation. These results demonstrate for the first time that NF-κB inhibition modulates mitochondrial dysfunction induced insulin resistance in 3T3-L1 adipocytes. View Full-Text
Keywords: adipocytes; mitochondrial dysfunction; inflammation; oxidative stress; insulin resistance; celastrol; nuclear factor kappa B (NF-κB) adipocytes; mitochondrial dysfunction; inflammation; oxidative stress; insulin resistance; celastrol; nuclear factor kappa B (NF-κB)
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Bakar, M.H.A.; Sarmidi, M.R.; Kai, C.K.; Huri, H.Z.; Yaakob, H. Amelioration of Mitochondrial Dysfunction-Induced Insulin Resistance in Differentiated 3T3-L1 Adipocytes via Inhibition of NF-κB Pathways. Int. J. Mol. Sci. 2014, 15, 22227-22257.

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