Lower Fasted State but Greater Change in Plasma Amino Acid-Induced Rise in Muscle Protein Synthesis in People with Obesity

OBJECTIVE: Obesity alters protein metabolism in skeletal muscle, but consistent evidence is lacking. We compared muscle protein synthesis in adults with obesity to that 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/m(2)) and ten controls (age 35 ± 3 years; BMI 23 ± 1 kg/m(2)) received an infusion of L-[2,3,3,4,5,5,5,6,6,6-(2)H(10)]leucine (0.15 μmol/kg FFM/min) to measure muscle protein synthesis after an overnight fast and during amino acid infusion. RESULTS: Despite greater muscle mTOR 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 S6K1 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.