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

Abstract

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-[2,3,3,4,5,5,5,6,6,6-² H₁₀ ]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.

Trial registration: ClinicalTrials.gov NCT01824173.

Figure 1

Blood leucine enrichment. Blood d₉-leucine enrichment in the course of the experimental protocol associated with the fasted state and elevated plasma amino acid concentrations (i.e., amino acids). MPE, molar percent excess.

Figure 2

Synthesis rate of skeletal muscle proteins. Synthesis rates of mixed-muscle (A) and muscle mitochondrial (B) proteins in the fasted state and during elevated plasma amino acids (i.e., AA). The bars to the right of the dotted line show the change (i.e., amino acids minus the fasted state) in the synthesis rate of mixed-muscle (A) and muscle mitochondrial (B) proteins in response to elevated plasma amino acid concentrations. Values represent the mean ± SEM. *P ≤ 0.05 versus lean subjects, ^†P ≤ 0.05 versus fasted state.

Figure 3

Skeletal muscle mTOR pathway signaling. Muscle mTOR (A) and S6K1 (B) phosphorylation in the fasted state and during elevated plasma amino acids (i.e., AA). The bars to the right of the dotted line show the fold change (i.e., amino acids divided by the fasted state) in mTOR (A) and S6K1 (B) phosphorylation in response to elevated plasma amino acid concentrations. Representative Western blots are shown. Dividing lines between blots indicate blots from different gels or different parts of the same gel. Values represent the mean ± SEM. *P ≤ 0.05 versus lean subjects, ^†P ≤ 0.05 versus fasted state.

Figure 4

Skeletal muscle eIF2α phosphorylation. Muscle eIF2α phosphorylation in the fasted state and during elevated plasma amino acids (i.e., AA). The bars to the right of the dotted line show the fold change (i.e., amino acids divided by the fasted state) in eIF2α phosphorylation in response to elevated plasma amino acid concentrations. Representative Western blots are shown. Values represent the mean ± SEM.

Figure 5

Skeletal muscle PGC1α mRNA and protein expression. Muscle PGC1α mRNA (A) and protein (B) expression in the fasted state and during elevated plasma amino acids (i.e., AA). The bars to the right of the dotted line show the fold change (i.e., amino acids divided by the fasted state) in muscle PGC1α mRNA (A) and protein (B) expression in response to elevated plasma amino acid concentrations. Representative Western blots are shown for PGC1α protein expression (B). Dividing lines between blots indicate blots from different gels or different parts of the same gel. Values represent the mean ± SEM. *P ≤ 0.05 versus lean subjects, ^†P ≤ 0.05 versus fasted state.