LOSS OF FATTY-ACID CONTROL OF GLUCONEOGENESIS AND PDH COMPLEX FLUX INADRENALECTOMIZED RATS

This work aimed to determine the role played by the adrenal gland in t he fatty acid control of gluconeogenesis in isolated perfused rat live rs. The gluconeogenic substrate concentration responses were not alter ed in adrenalectomized (ADX) rats. This observation indicates that glu cocorticoids are not essential to maintain normal basal gluconeogenic rates. In contrast, fatty acid failed to stimulate gluconeogenesis fro m lactate and elicited attenuated stimulation with pyruvate as substra te in livers from ADX rats. Fatty acid-induced stimulation of respirat ion and ketone body production were similar in control and ADX rats. T hus the diminished responsiveness of the gluconeogenic pathway to fatt y acid cannot be the result of different rates of energy production an d/or generation of reducing power. Fatty acids did not inhibit pyruvat e decarboxylation in livers from ADX rats. Even though mitochondria is olated from livers of ADX rats showed normal basal rates of pyruvate m etabolism, fatty acids failed to inhibit pyruvate decarboxylation and the activity of the pyruvate dehydrogenase complex. This novel observa tion of the glucocorticoid effect in controlling the pyruvate dehydrog enase complex responsiveness indicates that the mitochondrial partitio ning of pyruvate between carboxylation and decarboxylation reactions m ay be altered in livers from ADX rats. We propose that the diminished effect of fatty acid in stimulating gluconeogenesis in livers from ADX rats is the result of a limited pyruvate availability for the carboxy lase reaction due to a lack of inhibition of flux through the pyruvate dehydrogenase complex.