Tran, Lee

New Findings What is the central question of this study? Humans with obesity have lower ATP synthesis in muscle along with lower content of the β‐subunit of the ATP synthase (β‐F1‐ATPase), the catalytic component of the ATP synthase. Does lower synthesis rate of β‐F1‐ATPase in muscle contribute to these responses in humans with obesity? What is the main finding and its importance? Humans with obesity have a lower synthesis rate of β‐F1‐ATPase and ATP synthase specific activity in muscle. These findings indicate that reduced production of subunits forming the ATP synthase in muscle may contribute to impaired generation of ATP in obesity. AbstractThe content of the β‐subunit of the ATP synthase (β‐F1‐ATPase), which forms the catalytic site of the enzyme ATP synthase, is reduced in muscle of obese humans, along with a reduced capacity for ATP synthesis. We studied 18 young (37 ± 8 years) subjects of which nine were lean (BMI = 23 ± 2 kg m−2) and nine were obese (BMI = 34 ± 3 kg m−2) to determine the fractional synthesis rate (FSR) and gene expression of β‐F1‐ATPase, as well as the specific activity of the ATP synthase. FSR of β‐F1‐ATPase was determined using a combination of isotope tracer infusion and muscle biopsies. Gene expression of β‐F1‐ATPase and specific activity of the ATP synthase were determined in the muscle biopsies. When compared to lean, obese subjects had lower muscle β‐F1‐ATPase FSR (0.10 ± 0.05 vs. 0.06 ± 0.03% h−1; P < 0.05) and protein expression (P < 0.05), but not mRNA expression (P > 0.05). Across subjects, abundance of β‐F1‐ATPase correlated with the FSR of β‐F1‐ATPase (P < 0.05). The specific activity of muscle ATP synthase was lower in obese compared to lean subjects (0.035 ± 0.004 vs. 0.042 ± 0.007 arbitrary units; P < 0.05), but this difference was not significant after the activity of the ATP synthase was adjusted to the β‐F1‐ATPase content (P > 0.05). Obesity impairs the synthesis of β‐F1‐ATPase in muscle at the translational level, reducing the content of β‐F1‐ATPase in parallel with reduced capacity for ATP generation via the ATP synthase complex.

ObjectiveObesity 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.MethodsTen 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.ResultsDespite 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).ConclusionsAdults 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.

Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change ( P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased ( P < 0.01) whole body phenylalanine rate of appearance (μmol·kg−1·min−1), indicating suppression of muscle proteolysis, in both the control (1.02 ± 0.04 vs 0.76 ± 0.04) and the BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments ( P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA.