Context: Obesity-related insulin resistance of glucose and lipid metabolism may also affect protein kinetics, notably at the muscle level.

Objective: We hypothesized that muscle protein response to insulin and amino acid is blunted during obesity.

Research Design and Methods: Total (Tot) and mitochondrial (Mit) muscle proteins fractional synthesis rates (FSR) together with whole-body protein kinetics (WB) have been determined in postabsorptive state (PA) and during a hyperinsulinemic, hyperaminoacidemic, euglycemic clamp by using a continuous infusion of ¹³C-leucine in six obese and eight nonobese subjects.

Results: Responses of WB glucose disposal rate and protein breakdown to insulin and amino acid infusion were significantly lower in obese than in nonobese subjects (P < 0.05). In PA, Tot and Mit FSR were significantly lower (P < 0.05) in obese (Tot, 0.044 � 0.005% � h⁻¹; Mit, 0.064 � 0.008% � h⁻¹) in comparison with nonobese subjects (Tot, 0.082 � 0.010% � h⁻¹; Mit, 0.140 � 0.006% � h⁻¹). Tot FSR was similarly stimulated by insulin and amino acid in both groups (0.094 � 0.013 vs. 0.117 � 0.006% � h⁻¹, obese vs. nonobese; P < 0.05). Mit FSR was increased in nonobese subjects (0.179 � 0.007% � h⁻¹; P < 0.05) but not in obese subjects (0.078 � 0.012% � h⁻¹; P = not significant).

Conclusions: The obesity-related impairment of protein metabolism is characterized by 1) a reduced turnover rate of skeletal muscle proteins in PA; 2) a lack of stimulation of mitochondrial protein synthesis by insulin and amino acid; and 3) a lower inhibition of WB proteolysis by insulin and amino acid. Alterations of selective muscle protein kinetics may predispose obese subjects to muscle metabolic dysfunction leading to type 2 diabetes.