Protein metabolism in human obesity: Relationship with glucose and lipid metabolism and with visceral adipose tissue

It is controversial whether metabolic disorders of human obesity include protein metabolism. Even less information is available concerning the effect of fat distribution on protein metabolism. Therefore, a comprehensive evaluation of glucose, lipid, and protein metabolism was performed in 11 obese nondiabetic and 9 normal women whose body composition and regional fat distribution were determined. [1-¹⁴C]Leucine and [3-³H]glucose were infused in the postabsorptive state and during an euglycemic hyperinsulinemic (35-40 μU/mL) clamp combined with indirect calorimetry for assessment of leucine flux, oxidation, and nonoxidative disposal, glucose turnover and oxidation, and lipid oxidation. Fat-free mass (FFM) was estimated by a bolus of ³H₂O. Subcutaneous abdominal and visceral adipose tissues were determined by nuclear magnetic resonance imaging. During the clamp, obese women had lower glucose turnover (4.51 ± 0.41 vs. 6.63 ± 0.40 mg/min · kg FFM; P < 0.05), with a defect in both oxidation (3.27 ± 0.22 vs. 3.89 ± 0.21) and nonoxidative disposal (1.24 ± 0.27 vs. 2.74 ± 0.41; P < 0.005), whereas lipid oxidation was higher during the clamp (0.49 ± 0.15 vs. 0.17 ± 0.09 mg/min · kg FFM). There was no difference in leucine flux (basal, 2.23 ± 0.17 vs. 2.30 ± 0.29; clamp, 2.06 ± 0.19 vs. 2.10 ± 0.24 μmol/min · kg FFM), oxidation (basal, 0.37 ± 0.04 vs. 0.36 ± 0.05; clamp, 0.34 ± 0.04 vs. 0.39 ± 0.06) and nonoxidative leucine disposal (basal, 1.86 ± 0.17 vs. 1.94 ± 0.26; clamp, 1.72 ± 0.20 vs. 1.71 ± 0.19) in the two groups. In obese women, basal leucine oxidation was directly related with glucose oxidation and inversely to lipid oxidation (both P < 0.05), whereas visceral adipose tissue was inversely related to leucine flux both in the basal state and during the clamp (P < 0.05). In conclusion, in human obesity, 1) rates of protein metabolism in the basal state and in the range of insulin concentrations encountered after a meal are normal; 2) protein oxidation is positively related to glucose oxidation and negatively related to lipid oxidation; and 3) visceral adipose tissue is inversely related to all parameters of protein metabolism.