Changes in basal and insulin and amino acid response of whole body and skeletal muscle proteins in obese men

Abstract

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. Copyright © 2009 by The Endocrine Society.