Comprehensive Assessment of the Effects of Sleeve Gastrectomy on Glucose, Lipid, and Amino Acid Metabolism in Asian Individuals with Morbid Obesity.

Abstract

Obesity-induced insulin resistance leads to abnormalities in glucose, lipid, and amino acid metabolism. Our study examined the differences in insulin-mediated glucose, amino acid, and lipid metabolism between morbidly obese subjects with non-obese controls and the associated changes following sleeve gastrectomy (SG). Non-obese controls and individuals with morbid obesity and scheduled for SG were recruited. Metabolic assessments were performed for all subjects at baseline and at 6months after SG for eight subjects. The hyperinsulinemic-euglycemic clamp technique together with comprehensive metabolomic profiling was used to quantify insulin-mediated glucose, amino acid, and lipid metabolism. Eleven morbidly obese non-diabetic subjects scheduled for SG and nine non-obese controls were recruited. Compared to controls, obese subjects had significantly lower glucose uptake (4.4 ± 0.6 vs. 17.3 ± 2.4mg/kg FFM/min per μU/mL·100) and higher concentration of branched-chain amino acids (BCAAs, 332.5 ± 26.8 vs. 235.3 ± 11.0μM), non-esterified fatty acid (52.9 ± 9.9 vs. 25.6 ± 6.7μM), and lipid-related acylcarnitines (intermediate chain 389.8 ± 32.5 vs. 285.9 ± 20.5; long chain 301.7 ± 22.1 vs. 236.0 ± 13.3nM) during insulin clamp. Body weight significantly reduced at 6months after bariatric surgery (92.5 ± 6.3 vs. 115.2 ± 6.9kg), together with improvements in insulin-mediated glucose uptake, and suppression of BCAAs, non-esterified fatty acids, and lipid-related metabolites. Morbid obesity in Asian individuals was associated with impairment in the regulatory actions of insulin on glucose, amino acid, and lipid metabolism, and these obesity-induced regulatory dysfunctions improved significantly 6months after SG.