Context: Although moderate weight reduction is recommended as primary therapy of metabolic syndrome, little information is known regarding metabolic changes associated with moderate weight reduction in nondiabetic obese subjects.

Objective: The aim of this study was to determine the effects of a moderate weight reduction program on intracellular lipid and glucose metabolism in muscle and liver.

Participants: Data for 13 nondiabetic obese subjects were evaluated.

Intervention: Subjects were put on a 3-month mildly hypocaloric diet therapy (∼35 kcal/kg of ideal body weight).

Main Outcome Measures: Intrahepatic lipid (IHL) and intramyocellular lipid were measured by using ¹H magnetic resonance spectroscopy. Peripheral insulin sensitivity and splanchnic glucose uptake were evaluated by euglycemic-hyperinsulinemic clamp with oral glucose load.

Results: Diet therapy for 3 months resulted in 6% reduction in body weight (from 99.9 ± 7.3 to 93.8 ± 6.6 kg, P < 0.0001). This change was accompanied by reduction of plasma glucose and insulin excursions during 75-g oral glucose tolerance tests, decrease in diastolic blood pressure, glycated hemoglobin, serum low-density lipoprotein cholesterol, and triglyceride. These changes were also accompanied by a decrease in IHL (from 12.9 to 8.2%, P < 0.01) and increase in splanchnic glucose uptake (from 13.5 to 35.0%, P < 0.03). On the other hand, the diet program did not affect intramyocellular lipid or glucose infusion rate during euglycemic hyperinsulinemic clamp.

Conclusions: Our results suggest that moderate weight reduction in obese subjects decreased IHL and augmented splanchnic glucose uptake. This mechanism is at least in part involved in improvement of glucose metabolism by moderate weight reduction in obese subjects.