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Changes in Basal and Insulin and Amino Acid Response of Whole Body and Skeletal Muscle Proteins in Obese Men

Université Clermont 1 (C.Gu., Y.B.), Unité de Formation et de Recherche Médecine, Unité Mixte de Recherche (UMR) 1019, Centre de Recherche en Nutrition Humaine-Auvergne, Clermont-Ferrand, F-63009 France; Centre Hospitalier Universitaire Clermont-Ferrand (I.D., Y.B.), Hospital Gabriel Montpied, Clinical Nutrition Unit, Clermont-Ferrand, F-63001 France; Laboratory of Exercise Biology (M.R., M.B., P.D.), Auvergne and Blaise-Pascal University, Clermont-Ferrand, F-63000 France; and Institut National de la Recherche Agronomique, UMR 1019 (C.Gi., S.W., Y.B.), Clermont-Ferrand, F-63009 France

Address all correspondence and requests for reprints to: Christelle Guillet, Ph.D., Univ Clermont 1, Unité de Formation et de Recherche Médecine, Unité Mixte de Recherche 1019, Laboratoire de Nutrition Humaine, BP 321, 58 rue Montalembert, 63009 Clermont-Ferrand cedex 1, France. E-mail: cguillet{at}clermont.inra.fr.

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.