Lower Fasted-State but Greater Increase in Muscle Protein Synthesis in Response to Elevated Plasma Amino Acids in Obesity

Objective: Obesity alters protein metabolism in skeletal muscle, but consistent evidence is lacking. This study compared muscle protein synthesis in adults with obesity and in lean controls in the fasted state and during an amino acid infusion. Methods: Ten subjects with obesity (age: 36 ± 3 years; BMI: 34 ± 1 kg/m²) and ten controls (age: 35 ± 3 years; BMI: 23 ± 1 kg/m²) received an infusion of L-[2,3,3,4,5,5,5,6,6,6-²H₁₀]leucine (0.15 μmol/kg fat-free mass/min) to measure muscle protein synthesis after an overnight fast and during amino acid infusion. Results: Despite greater muscle mammalian target of rapamycin phosphorylation (P ≤ 0.05), fasted-state mixed-muscle and mitochondrial protein synthesis were lower in subjects with obesity (P ≤ 0.05). However, the change in mixed-muscle protein synthesis during the amino acid infusion was 2.7-fold greater in subjects with obesity (P ≤ 0.05), accompanied by a greater change in S6 kinase-1 phosphorylation (P ≤ 0.05). The change in mitochondrial protein synthesis did not differ between groups (P > 0.05). Conclusions: Adults with obesity have reduced muscle protein synthesis in the fasted state, but this response is compensated for by a greater change in overall muscle protein synthesis during amino acid infusion.