Lactate disposal via gluconeogenesis is increased during exercise in patients with mitochondrial myopathy due to complex I deficiency

Abstract

This study evaluated lactate disposal via gluconeogenesis as well as effects of FFA availability on gluconeogenesis via pyruvate (GNGPYR) in patients with mitochondrial myopathy due to complex I deficiency (CID). The rates of GNGPYR were measured in three CID patients and six healthy controls at rest and during 90 min cycle exercise, using the deuterium-labeled water method. All subjects served as their own control: on one occasion they were studied in the fasting state, and on the second occasion they received an infusion of triacylglycerol plus heparin. At rest, the fractional rate of gluconeogenesis from pyruvate was higher in patients than in controls in the fasting state. Triacylglycerol infusion was associated with increased rates of GNGPYR at rest in controls (p < 0.05) but not in patients. Circulating lactate and pyruvate levels were increased 3-fold during exercise in the CID patients. During exercise, GNGPYR increased in the CID patients (p < 0.01) and remained unchanged in controls, resulting in 85% and 72% higher absolute rates of GNGPYR in the patients than in the controls during fasting and triacylglycerol infusion, respectively. During exercise, rates of GNGPYR were not different between fasting and triacylglycerol infusion within both groups. Our data show that 1) GNGPYR is increased during exercise in CID patients; 2) increased pyruvate availability contributes to the higher rates of GNGPYR in the CID patients; and 3) exogenous infusion of fatty acids is not associated with increased rates of GNGPYR in CID patients at rest or during exercise. GNGPYR is a significant mechanism of lactate disposal in exercising CID patients, but triglyceride infusion does not enhance their lactate disposal through this mechanism.