Fatty acyl-CoAs as feedback regulators of hexose monophosphate shunt in rat adipocytes

Abstract

The high basal glucose utilization through hexose monophosphate shunt found in our experimental conditions were almost completely inhibited by oleate, octanoate and caproate. However, the inhibition of glucose oxidation due to butyrate was about 50% whereas ketone bodies and acetate did not inhibit. The rate of triacylglycerol formation was not significantly modified with the above organic acids except oleate that presented a 5-fold increase on labeling incorporation into lipids. Oleate inhibition of glucose oxidation was completely prevented by the NADPH oxidant menadione. There was no inhibition by octanoate, caproate, butyrate or ketone bodies of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase or malic enzyme in adipose tissue homogenates. In contrast, specifically glucose-6-phosphate dehydrogenase was inhibited by oleoyl-CoA. The oleoyl-CoA inhibition was prevented by enzyme preincubation with low NADP concentration. The data lend further support for the hypothesis that fatty acids and NADP fulfill an important role in the modulation of the hexose monophosphate shunt activity.