NONESTERIFIED FATTY-ACIDS REGULATE LIPID AND GLUCOSE-OXIDATION AND GLYCOGEN-SYNTHESIS IN HEALTHY MAN

We examined the interrelationship of lipid and glucose metabolism in the basal state and during insulin stimulus in 19 healthy men (27+/-2 years, body mass index 23.6+/-0.6 kg/m(2)). In each subject, we performed a 4-h euglycaemic (5.3+/-0.1 mmol/l) hyperinsulinaemic (647+/-21 pmol/l) insulin clamp with indirect calorimetry in the basal state and during insulin infusion, and muscle biopsies before and at the end of the clamp. In the basal state, serum non-esterified fatty acid levels correlated directly with lipid oxidation (r = 0.56, p < 0.05) and indirectly with glucose oxidation (r = -0.80, p < 0.001). Lipid and glucose oxidation rates were inversely related in the basal state (r = -0.47, p < 0.05) and during insulin infusion (r = -0.65, p < 0.01). Basal lipid oxidation and glycogen synthase total activity correlated inversely (r = -0.54, p < 0.05). Lipid oxidation both in the basal state (r = -0.61, p < 0.01) and during insulin infusion (r = -0.62, p < 0.05) was inversely related to muscle glycopen content after the insulin clamp. Fasting plasma triglyceride concentration correlated directly to fasting insulin (r = 0.55, p < 0.05) and C-peptide (r = 0.50, p < 0.03) concentrations and inversely to non-oxidative glucose disposal rate at the end of clamp (r = -0.54, p < 0.05). In conclusion: 1) Serum non-esterified fatty acid concentration enhances lipid and reduces glucose oxidation. 2) Lipid oxidation is inversely related to total glycogen synthase activity. 3) Lipid oxidation both in the basal state and during insulin stimulus correlates inversely with muscle glycogen content after insulin infusion. 4) Even in normotriglyceridaemic subjects, plasma triglycerides reduce insulin-stimulated non-oxidative glucose disposal. These data suggest that serum non-esterified fatty acids in physiologic concentrations have an important role in the regulation of lipid and glucose oxidation as well as glucose storage as glycogen.