The provision of a high-fat diet (47% of energy as fat) for 28 days led to a significant increase in hepatic
pyruvate dehydrogenase kinase activity, together with significant suppression of hepatic
pyruvate dehydrogenase (active form). An enhanced hepatic
pyruvate dehydrogenase kinase activity continued to be observed at 6 h after the withdrawal of the high-fat diet. Significant suppression of hepatic
pyruvate dehydrogenase kinase activity was observed in post-absorptive, high-fat-fed rats after a 2.5 h euglycaemic-hyperinsulinaemic clamp, such that differences in
pyruvate dehydrogenase kinase activities between control and high-fat-fed rats were no longer evident.
Starvation for 24 h in rats previously maintained on standard diet also evoked a substantial increase in hepatic
pyruvate dehydrogenase kinase activity. This latter response was only partially reversed by 2.5 h of euglycaemic hyperinsulinaemia. Suppression of
pyruvate dehydrogenase kinase activity by 2.5 h euglycaemic hyperinsulinaemia in high-fat-fed rats was associated with a substantial increase in hepatic
pyruvate dehydrogenase activity (active form) whereas no significant increase in hepatic
pyruvate dehydrogenase activity (active form) was observed after 2.5 h euglycaemic hyperinsulinaemia in 24 h-starved rats. The results are consistent with the proposition that hepatic
pyruvate dehydrogenase kinase responds directly to an increase in
lipid oxidation which is facilitated by
insulin deficiency or an impaired action of
insulin.