Increased glycolysis is an early consequence of palmitate lipotoxicity mediated by redox signaling

Exposure to toxic levels of fatty acids (lipotoxicity) leads cell damage and death is involved in the pathogenesis metabolic syndrome. Since consequences lipotoxicity are still poorly understood, we studied bioenergetic effects saturated acid palmitate, quantifying changes mitochondrial morphology, real-time oxygen consumption, ATP production sources, extracellular acidification hepatoma cells. Surprisingly, glycolysis was enhanced by presence palmitate as soon 1 h after stimulus, while consumption oxidative phosphorylation were unchanged, despite overt fragmentation. Palmitate only induced fragmentation if glucose glutamine available, glycolytic enhancement did not require glutamine, showing it independent morphological changes. Redox state altered indicated NAD(P)H quantification. Furthermore, antioxidant mitoquinone, or a selective inhibitor complex I electron leakage (S1QEL) further palmitate-induced glycolysis. Our results demonstrate that overload involves an unexpected early increase flux, while, surprisingly, no observed. Interestingly, signaling mitochondrially-generated oxidants, uncovering novel regulatory mechanism for this pathway.