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J Clin Endocrinol Metab. 2009 Aug;94(8):3044-50. doi: 10.1210/jc.2008-2216. Epub 2009 May 26.

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

Author information

1
Unité de Formation et de Recherche Médecine, Unité Mixte de Recherche 1019, Laboratoire de Nutrition Humaine, Université Clermont 1, 58 rue Montalembert, Clermont-Ferrand cedex 1, France. cguillet@clermont.inra.fr

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 (13)C-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.

PMID:
19470633
DOI:
10.1210/jc.2008-2216
[Indexed for MEDLINE]

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