Mitochondrial dysfunction of 3t3-l1 adipocytes induced by oligomycin and antimycin a

• Main Author: Wan Hassan @Wan Hussein, Wan Najihah (Author)
• Format: Thesis
• Published: 2015.
• Subjects: TP Chemical technology; Thesis
• Online Access: Get fulltext

 There are accumulating evidence showing that mitochondrial dysfunction is strongly associated with impaired insulin release and its actions in peripheral tissues. Adipose tissue is one of the important peripheral tissues that regulate the whole-body glucose homeostasis. Metabolic imbalance of energy productions and impaired oxidative phosphorylation in this tissue may lead to mitochondrial dysfunction. The present study sought to investigate the metabolic profile of 3T3-L1 adipocytes in the event of mitochondrial dysfunction. The induction of mitochondria dysfunction in adipocytes were performed by using treatment of oligomycin and antimycin A (AA). Cell viability, triglyceride accumulation, glucose utilization and adenosine triphosphate (ATP) production were analyzed following treatment with these inhibitors. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to identify the alteration of metabolic profiles associated with mitochondrial dysfunction in adipocytes. The result showed that oligomycin and AA treatment dramatically decreased cell viability by inducing mitochondrial dysfunction at the dose of 8 µM and 0.0128 µM, respectively. The treated cells were found to exhibit increased intracellular accumulation of lipid droplets. Both inhibitors significantly reduced glucose utilization and concomitantly impaired ATP production in adipocytes. Importantly, metabolic profile of adipocytes with mitochondrial dysfunction identified glycerol, arachidonic acid, glutamic acid, ceramide and glycerolphosphoethanolamine (GPE) as predictors for such metabolic perturbations. These findings underscore the potential role of intracellular metabolite in pathogenesis of insulin resistance, thereby suggesting that mitochondrial dysfunction could aid in risk assessment of diabetes.