Obesity-related disruption in lipid metabolism contributes to cardiovascular dysfunction. Despite numerous studies on lipid metabolism in the left ventricle, there is no data describing the influence of
n-acetylcysteine (NAC) and α-
lipoic acid (ALA), as
glutathione precursors, on
sphingolipid metabolism, and
insulin resistance (IR) occurrence. The aim of our experiment was to evaluate the influence of chronic
antioxidants administration on myocardial
sphingolipid state and intracellular
insulin signaling as a potential therapeutic strategy for
obesity-related cardiovascular IR. The experiment was conducted on male Wistar rats fed a standard rodent chow or a high-fat diet with intragastric administration of NAC or ALA for eight weeks. Cardiac and plasma
sphingolipid species were assessed by high-performance liquid chromatography (HPLC). The
proteins expressed from
sphingolipid and
insulin signaling pathways were determined by Western blot.
Antioxidant supplementation markedly reduced
ceramide accumulation by lowering the expression of selected
proteins from the
sphingolipid pathway and simultaneously increased the myocardial
sphingosine-1-phosphate level. Moreover, NAC and ALA augmented the expression of GLUT4 and the phosphorylation state of Akt (Ser473) and GSK3β (Ser9), which improved the intracellular
insulin transduction pathway. Based on our results, we may postulate that NAC and ALA have a beneficial influence on the cardiac ceramidose under IR conditions.