Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kappa B pathways
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. Neve...
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2014
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| author | Abu Bakar, M.H. Sarmidi, M.R. Kai, C.K. Huri, H.Z. Yaakob, H. |
| author_facet | Abu Bakar, M.H. Sarmidi, M.R. Kai, C.K. Huri, H.Z. Yaakob, H. |
| author_sort | Abu Bakar, M.H. |
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| content_provider | Universiti Malaya |
| content_source | UM Research Repository |
| continent | Asia |
| country | Malaysia |
| description | 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. |
| format | Article |
| id | my.um.eprints-15565 |
| institution | Universiti Malaya |
| publishDate | 2014 |
| publisher | MDPI AG |
| record_format | eprints |
| spelling | my.um.eprints-155652016-01-28T01:39:28Z http://eprints.um.edu.my/15565/ Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kappa B pathways Abu Bakar, M.H. Sarmidi, M.R. Kai, C.K. Huri, H.Z. Yaakob, H. Q Science (General) 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. MDPI AG 2014 Article PeerReviewed 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. |
| spellingShingle | Q Science (General) Abu Bakar, M.H. 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-kappa B pathways |
| title | Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kappa B pathways |
| title_full | Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kappa B pathways |
| title_fullStr | Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kappa B pathways |
| title_full_unstemmed | Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kappa B pathways |
| title_short | Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-kappa B pathways |
| title_sort | amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3t3-l1 adipocytes via inhibition of nf-kappa b pathways |
| topic | Q Science (General) |
| url | http://eprints.um.edu.my/15565/ |
| url_provider | http://eprints.um.edu.my/ |