Endocrine Abstracts

Background: Branched-chain amino acids (BCAA) are elevated in morbid obesity and decreases significantly following bariatric surgery. This decrease is associated with the post-surgical improvement in insulin resistance (IR) and may be secondary to the reduction in BCAA flux from proteolysis or an increase in BCAA catabolism. Presently, the underlying mechanism is unclear.

Aim: To investigate the changes in BCAA metabolism in morbidly obese individuals following bariatric surgery.

Hypothesis: The decrease in plasma BCAA after bariatric surgery is due to the improved ability of insulin to suppress BCAA flux from proteolysis.

Methods: 11 morbidly obese non-diabetic subjects scheduled for sleeve gastrectomy and 9 healthy non-obese controls were recruited. Metabolic assessments were performed for all subjects at baseline and at 6 months for the surgical subjects. IR was quantified as the insulin sensitivity index (ISI) obtained using the hyperinsulinemic-euglycemic clamp method and plasma BCAA and short-chain acyl-carnitines (ACs) were measured using mass spectrometry during fasting and insulin clamp.

Results: Morbidly obese subjects were significantly more insulin resistant than controls at baseline with a lower ISI (4.39±1.95 vs 17.27±7.31 mg/kgFFM per min per μU/ml·100). Following surgery, there were significant reductions in weight (114.80±22.64 to 91.90±16.65 kg), BMI (39.09±4.68 to 31.29±2.91 kg/m²) and increase in ISI (4.39±1.95 to 13.68±3.36 mg/kgFFM per min per μU/ml·100). Plasma BCAA in morbidly obese subjects were similar to controls during fasting, but decreased to a greater extent in the control group following insulin infusion such that BCAA levels measured during the insulin clamp were significantly higher in the morbidly obese (332.47±88.77 vs 235.32±33.00 μM). However, no difference in short-chain ACs between the two groups was found. Interestingly, plasma BCAA during fasting and insulin clamp both decreased significantly (fasting BCAA 445.37±75.21 to 326.19±54.88 μM; insulin clamp BCAA 332.47±88.77 to 211.56±44.16 μM) following bariatric surgery but also without any changes in short-chain ACs levels.

Conclusion: The impaired ability of insulin to suppress BCAA flux is responsible for the higher plasma BCAA level in morbidly obese individuals during insulin clamp at baseline while the decrease in BCAA following bariatric surgery can be attributed to the improvement in insulin-mediated suppression of branched-chain amino acid flux. BCAA catabolism by contrast did not play an important role.