Mitochondrial dysfunctions enhances lipolysis and intracellular lipid accumulation in 3t3-l1 adipocytes

Abstract

Adipose tissue is one of the important peripheral tissues that regulate the whole-body homeostasis. Metabolic imbalance of energy productions and impaired oxidative phosphorylation in this target tissue may lead to mitochondrial dysfunction. However, it is currently unknown, what is the effect of mitochondrial dysfunctions in adipocytes on the cellular lipolysis activities and intracellular lipid accumulations. In this study, we determined the direct effects of mitochondrial dysfunction on the lipolysis activity and relative distribution of lipids in adipocytes. The induction of mitochondrial dysfunctions in adipocytes was performed with the treatment of two common mitochondrial respiratory inhibitors, antimycin A (Complex III) and oligomycin (ATP synthase) on 3T3-L1 adipocytes. We found that in the presence and absence of insulin, both respiratory inhibitors significantly reduced intracellular ATP concentrations within adipocytes. Furthermore, both drug treatments resulted in the significant elevation of free fatty acids and glycerol release into the media compared to control. The treated cells were also found to exhibit an irregular intracellular accumulation of lipid droplets. Our result demonstrated that lipolysis activity, and abnormal intracellular lipid accumulations were up-regulated in the event of mitochondrial dysfunctions in adipocytes, warranting further research are required for studying mechanisms underlying these metabolic impairments.