Vanillic acid retains redox status in HepG2 cells during hyperinsulinemic shock using the mitochondrial pathway

Abstract

Vanillic acid (VA) is a flavoring and nutritional agent found in many fruits and vegetables. It is an antioxidant but its nutraceutical potential has not been studied in detail. In this study, the potential of VA against hyperinsulinemia mediated changes on redox status and mitochondria in HepG2 cells were investigated. Incubation of cells with 1 μM insulin for 24 h was found to induce insulin resistance using the inhibition of Glut2 and glucose uptake (51.9%). Hyperinsulinemia caused depletion of superoxide dismutase, glutathione, glutathione peroxidase and generation of reactive oxygen species (68%). It also caused overexpression of the receptor for advanced glycation end products (120%) and a decreases of dolichyl-diphospho-oligosaccharide-protein glycosyltransferase non-catalytic subunit (34%). Mitochondria were affected with alterations in mitochondrial transmembrane potential, aconitase activity, mitochondrial fission and fusion, biogenesis (AMPK, Sirt1 and PGC-1α) and bioenergetics (ATP and oxygen consumption). Co-treatment with VA decreased oxidative stress by reducing reactive oxygen species and lipid peroxidation during hyperinsulinemia. Similarly, VA protected the mitochondria during insulin shock. VA also prevented glycation through the decrease of the receptor for advanced glycation end products expression. VA was found to act through the AMPK/Sirt1/PGC-1α pathway to obtain its beneficial activity. From the overall results it was concluded that VA is expected to be a potential nutraceutical which could be explored for the development of affordable nutraceuticals after detailed in vivo study.