The effect of changes in lipid oxidation on glucose utilization (storage and oxidation) was studied in seven nondiabetic obese patients. They participated in three protocols in which: (1) Intralipid (to raise plasma FFA concentrations), (2) -pyridylcarbinol [a precursor of nicotinic acid, to lower plasma free fatty acids (FFA) concentrations], or (3) isotonic saline were infused over 2 h. Thereafter, these infusions were discontinued, and a 2-h cuglycemic, hyperinsulinemic clamp was performed to measure glucose uptake. All studies were carried out in combination with indirect calorimetry to measure oxidative and nonoxidative glucose disposal (glucose storage). The high plasma FFA concentrations (1024±57 mol/l) and lipid oxidation rates (1.1±0.1 mg/kg·min) found at the end of the Intralipid infusion and the low plasma FFA concentrations (264±26 mol/l and lipid oxidation rates 0.7±0.1 mg/kg·min) found at the end of the -pyridylcarbinol infusions resulted in significantly different rates of total and nonoxidative glucose disposal during the insulin clamp. The values were 2.6±0.6 mg/kg·min after Intralipid and 4.1±1.0 mg/kg·min after -pyridylcarbinol for total glucose disposal, and 0.4±0.4 and 1.6±0.8, respectively for nonoxidative glucose disposal. In conclusion, these observations show that changes in lipid oxidation rates preceding a glucose load influence glucose disposal and glycogen storage in obese subjects.