Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways
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. Neverthel...
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my.utm.517562018-10-21T04:33:32Z http://eprints.utm.my/id/eprint/51756/ Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways Abu Bakar, Mohamad Hafizi Sarmidi, Mohamad Roji Cheng, Kian Kai Huri, Hasniza Zaman Ya’akob, Harisun QP Physiology 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 MDPI AG 2014 Article PeerReviewed application/pdf en http://eprints.utm.my/id/eprint/51756/1/MohamadHafiziAbuBakar2014_AMeliorationOfMitochondrialDysfunction.pdf Abu Bakar, Mohamad Hafizi and Sarmidi, Mohamad Roji and Cheng, Kian Kai and Huri, Hasniza Zaman and Ya’akob, Harisun (2014) Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways. International Journal of Molecular Sciences, 15 (12). pp. 22227-22257. ISSN 1661-6596 http://dx.doi.org/10.3390/ijms151222227 |
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QP Physiology Abu Bakar, Mohamad Hafizi Sarmidi, Mohamad Roji Cheng, Kian Kai Huri, Hasniza Zaman Ya’akob, Harisun Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways |
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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 |
format |
Article |
author |
Abu Bakar, Mohamad Hafizi Sarmidi, Mohamad Roji Cheng, Kian Kai Huri, Hasniza Zaman Ya’akob, Harisun |
author_facet |
Abu Bakar, Mohamad Hafizi Sarmidi, Mohamad Roji Cheng, Kian Kai Huri, Hasniza Zaman Ya’akob, Harisun |
author_sort |
Abu Bakar, Mohamad Hafizi |
title |
Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways |
title_short |
Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways |
title_full |
Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways |
title_fullStr |
Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways |
title_full_unstemmed |
Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways |
title_sort |
amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3t3-l1 adipocytes via inhibition of nf-κb pathways |
publisher |
MDPI AG |
publishDate |
2014 |
url |
http://eprints.utm.my/id/eprint/51756/1/MohamadHafiziAbuBakar2014_AMeliorationOfMitochondrialDysfunction.pdf http://eprints.utm.my/id/eprint/51756/ http://dx.doi.org/10.3390/ijms151222227 |
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1643653063438761984 |
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13.159267 |