Abu Bakar, M.H. and Sarmidi, M.R. and Kai, C.K. and Huri, H.Z. and Yaakob, H. (2014) Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kappa B pathways. International Journal of Molecular Sciences, 15 (12). pp. 22227-22257.
Full text not available from this repository.Abstract
A growing body of evidence suggests that activation of nuclear factor kappa B (NF-kappa B) 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-kappa B pathways in regulating mitochondrial function of the adipose tissues. In the present study, we sought to investigate the direct effects of celastrol (potent NF-kappa B 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-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) 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-kappa B 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-kappa B inhibition modulates mitochondrial dysfunction induced insulin resistance in 3T3-L1 adipocytes.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Adipocytes; mitochondrial dysfunction; inflammation; oxidative stress; insulin resistance; celastrol; nuclear factor kappa B (NF-kappa B) |
| Subjects: | Q Science > Q Science (General) |
| Depositing User: | Dr Mohd Faizal Hamzah |
| Date Deposited: | 28 Jan 2016 01:39 |
| Last Modified: | 28 Jan 2016 01:39 |
| URI: | http://eprints.um.edu.my/id/eprint/15565 |
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