Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.
Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.
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DOI：
10.1126/scitranslmed.3002043
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发表时间：
2011-04-27
影响因子：
17.1
通讯作者：
Newgard CB
中科院分区：
文献类型：
--
作者：
Laferrère B;Reilly D;Arias S;Swerdlow N;Gorroochurn P;Bawa B;Bose M;Teixeira J;Stevens RD;Wenner BR;Bain JR;Muehlbauer MJ;Haqq A;Lien L;Shah SH;Svetkey LP;Newgard CB
在病态肥胖和2型糖尿病患者中，胃旁路手术（GBP）后血糖控制比同等饮食诱导体重减轻后改善更多。我们应用代谢组学分析来了解GBP后这种更好的代谢反应的机制。通过靶向串联质谱法测定空腹受试者在服用GBP或饮食导致体重减轻10公斤前后血浆中的循环氨基酸（AAs）和酰基肉碱（ACs）。总AAs和支链AAs （BCAAs）在GBP后下降，但在饮食干预后没有下降。BCAA氧化产生的代谢物也仅在GBP后下降。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），另一个主要由BCAAs及其代谢物组成（PC2）。PC1和PC2与胰岛素前浓度、c肽对口服葡萄糖的反应以及减肥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）唯一相关。这些数据表明，GBP后循环AAs的增强下降是通过体重减轻以外的机制发生的，可能有助于手术干预中观察到的葡萄糖稳态的更好改善。
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.
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影响因子：
5.8
作者：
Laferrere, Blandine;Teixeira, Julio;Olivan, Blanca
通讯作者：
Olivan, Blanca
影响因子：
6.9
作者：
Mihalik, Stephanie J.;Goodpaster, Bret H.;Kelley, David E.;Chace, Donald H.;Vockley, Jerry;Toledo, Frederico G. S.;DeLany, James P.
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DeLany, James P.
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Roden, M
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作者：
Laferrere, Blandine;Heshka, Stanley;Olivan, Blanca
通讯作者：
Olivan, Blanca
影响因子：
120.7
作者：
Svetkey, Laura P.;Stevens, Victor J.;Aicher, Kathleen
通讯作者：
Aicher, Kathleen