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

• Published in: The journal of clinical endocrinology and metabolism 2009-08, Vol.94 (8), p.3044-3050
• Main Authors: Guillet, Christelle, Delcourt, Ingrid, Rance, Melanie, Giraudet, Christophe, Walrand, Stephane, Bedu, Mario, Duche, Pascale, Boirie, Yves
• Format: Article
• Language: English
• Subjects: Adult; Amino Acids - metabolism; Biological and medical sciences; Body Composition; Endocrinopathies; Fatty Acids, Nonesterified - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Humans; Insulin - blood; Insulin - pharmacology; Insulin Resistance; Leucine - metabolism; Life Sciences; Male; Medical sciences; Mitochondrial Proteins - metabolism; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Obesity - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-2216

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. Obesity is associated with disturbances of muscle protein metabolism, notably a reduced basal skeletal muscle and mitochondria protein turnover and a limited stimulatory action of insulin upon mitochondrial protein synthesis.