New York Obesity Nutrition Research Center, St. Luke's Roosevelt Hospital Center, New York, NY 10025, USA.
Sci Transl Med. 2011 Apr 27;3(80):80re2. doi: 10.1126/scitranslmed.3002043.
Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied metabolomic profiling to understand the mechanisms of this better metabolic response after GBP. Circulating amino acids (AAs) and acylcarnitines (ACs) were measured in plasma from fasted subjects by targeted tandem mass spectrometry before and after a matched 10-kilogram weight loss induced by GBP or diet. Total AAs and branched-chain AAs (BCAAs) decreased after GBP, but not after dietary intervention. Metabolites derived from BCAA oxidation also decreased only after GBP. Principal components (PC) analysis identified two major PCs, one composed almost exclusively of ACs (PC1) and another with BCAAs and their metabolites as major contributors (PC2). PC1 and PC2 were inversely correlated with pro-insulin concentrations, the C-peptide response to oral glucose, and the insulin sensitivity index after weight loss, whereas PC2 was uniquely correlated with levels of insulin resistance (HOMA-IR). These data suggest that the enhanced decrease in circulating AAs after GBP occurs by mechanisms other than weight loss and may contribute to the better improvement in glucose homeostasis observed with the surgical intervention.
胃旁路手术（GBP）后血糖控制的改善程度优于同等饮食诱导的肥胖合并 2 型糖尿病患者的体重减轻。我们应用代谢组学分析来了解 GBP 后这种更好代谢反应的机制。通过靶向串联质谱法，在 GBP 或饮食诱导的 10 公斤体重减轻前后，测量空腹受试者血浆中的循环氨基酸（AAs）和酰基辅酶 A（ACs）。GBP 后总 AAs 和支链氨基酸（BCAAs）降低，但饮食干预后没有降低。仅在 GBP 后，BCAA 氧化衍生的代谢物也降低。主成分（PC）分析确定了两个主要的 PC，一个几乎完全由 ACs 组成（PC1），另一个以 BCAAs 及其代谢物为主要贡献者（PC2）。PC1 和 PC2 与空腹胰岛素浓度、口服葡萄糖后的 C 肽反应以及体重减轻后的胰岛素敏感性指数呈负相关，而 PC2 与胰岛素抵抗水平（HOMA-IR）呈独特相关。这些数据表明，GBP 后循环 AAs 的增强降低不是通过体重减轻以外的机制发生的，并且可能有助于观察到手术干预后葡萄糖稳态的更好改善。
