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

International Journal of Molecular Sciences

Mohamad Hafizi Abu Bakar⁴  Mohamad Roji Sarmidi¹  Cheng Kian Kai⁴  Hasniza Zaman Huri²  Harisun Yaakob³ 

[1] Institute of Bioproduct Development, University Teknologi Malaysia, Skudai 81310, Malaysia;Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; E-Mail:;Innovation Centre in Agritechnology for Advanced Bioprocessing (ICA), University Teknologi Malaysia, Skudai 81310, Malaysia; E-Mail:;Department of Bioprocess Engineering, Faculty of Chemical Engineering, University Teknologi Malaysia, Skudai 81310, Malaysia; E-Mail:

关键词: adipocytes;    mitochondrial dysfunction;    inflammation;    oxidative stress;    insulin resistance;    celastrol;    nuclear factor kappa B (NF-κB);   

DOI  :  10.3390/ijms151222227

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.