Glycolysis inhibition by palmitate in renal cells cultured in a two-chamber system

A major shortcoming of renalproximal tubular cells (RPTC) in culture is the gradual modification oftheir energy metabolism from the oxidative type to the glycolytic type.To test the possible reduction of glycolysis by naturally occurringlong-chain fatty acids, RPTC were cultured in a two-chamber system,with albumin-bound palmitate (0.4 mM) added to the basolateral chamberafter confluency. Twenty-four hours of contact with palmitate decreasedglycolysis by 38% provided that carnitine was present;lactate production was decreased by 38%, and the decrease inglycolysis resulted from a similar decrease of basolateral and apicalnet uptake of glucose. In contrast to the previously described effectof the nonphysiological oxidative substrate heptanoate, palmitatepromoted a long-term decrease in lactate production and sustainedexcellent cellular growth. After 4 days of contact, decreasedglycolysis was maintained even in the absence of carnitine and resultedfrom a decrease of basolateral uptake only, suggestive of long-term regulation different from the earlier effects. Thus, although culturedRPTC lost their oxidative phenotype, they exhibited a type ofregulation (Randle effect) that is found in the oxidative-type but notin the glycolytic-type tissues, therefore unmasking a regulativecapacity barely detectable in fresh RPTC. LowPO₂ (50 mmHg in the apical chamber) could be amajor cause of elevated glycolysis and could hinder the effects ofpalmitate.