Mitochondrial ATP synthase β‐subunit production rate and ATP synthase specific activity are reduced in skeletal muscle of humans with obesity

The content of the beta 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 reduced capacity for ATP synthesis. We studied 18 young (37 ± 8 years old) subjects of which nine were lean (BMI = 23 ± 2 kg/m2) and nine were obese (BMI = 34 ± 3 kg/m2) 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 %/hr; P 0.05). Across subjects, abundance of β-F1-ATPase correlated with the FSR of β-F1-ATPase (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.