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




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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

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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.



Abstract 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





Author: Mohamad Hafizi Abu Bakar 1,* , Mohamad Roji Sarmidi 2,3,* , Cheng Kian Kai 1,3, Hasniza Zaman Huri 4,5 and Harisun Yaakob 3

Source: http://mdpi.com/



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