Insulin resistance by TNF-α is associated with mitochondrial dysfunction in 3T3-L1 adipocytes and is ameliorated by punicic acid, a PPARγ agonist.

Punicic acid (PA), a poly unsaturated fatty acid found abundantly in pomegranate seed oil is reported to have PPARγ agonist property. TNF-α mediated insulin resistance plays an important role in the pathogenesis of diabetes and is associated with severe mitochondrial impairment. In this study, PA was evaluated for its ability to ameliorate TNF-α induced mitochondrial dysfunctions in 3T3-L1 adipocytes. For this, we examined the alterations in mitochondrial energetics, biogenesis, transmembrane potential and dynamics in TNF-α induced insulin resistant model of 3T3-L1 adipocytes. PA improved glucose uptake, ROS accumulation, mitochondrial biogenesis and energetics in TNF-α treated cells. In addition, treatment with PA was found to ameliorate TNF-α induced alterations in proteins associated with mitochondrial dynamics like FIS1 and OPA1. These findings suggest that PA can be considered as an active lead for the management of insulin resistance and associated mitochondrial dysfunctions.