Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism
Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism
复制标题
DOI：
10.1152/ajpendo.00134.2007
复制
发表时间：
2007-12-01
影响因子：
5.1
通讯作者：
Lynch, Christopher J.
中科院分区：
文献类型：
--
作者：
She, Pengxiang;Van Horn, Cynthia;Lynch, Christopher J.
She P，范霍恩C，Reid T，Hutson SM，Cooney RN，Lynch CJ.肥胖相关的血浆亮氨酸升高与支链氨基酸代谢酶的改变有关。Am J Physiol Endocrinol Metab 293：E1552-E1563，2007.首次发表于2007年10月9日; doi：10.1152/ajpendo.00134.2007。人类肥胖症中支链氨基酸（BCAA）的升高最早是在20世纪60年代报道的。这些报告是感兴趣的，因为支链氨基酸作为饱腹感，瘦素，葡萄糖，细胞信号传导，肥胖和体重（mTOR和PKC）的潜在调节剂的新兴作用。为了探索分解代谢能力的丧失作为肥胖相关的支链氨基酸升高的潜在贡献者，我们评估了两种肥胖啮齿动物模型（ob/ob小鼠和Zucker大鼠）和人类手术减肥干预后线粒体支链氨基酸转氨酶（BCATm）或支链α-酮酸脱氢酶（BCKD E1 α亚基）复合物催化的前两个酶促步骤。肥胖啮齿动物表现出高氨基酸血症，包括支链氨基酸。尽管在啮齿动物骨骼肌BCATm、pS293或总BCKD E1 α或BCKD激酶中未观察到肥胖相关变化，但在肝脏中，BCKD E1 α未因肥胖而改变或减少，pS293（与BCKD的非活动状态相关）与BCKD激酶一起沿着增加。在附睾脂肪中，观察到BCATm和BCKD E1 α与肥胖相关的下降。血浆支链氨基酸减少了一夜之间的快速与脂肪组织中的变化，但不是在肝脏中的消散相一致。在纵向研究的人类受试者中，通过手术减肥干预（Roux-en-Y胃旁路术）也降低了BCAA。这些变化与网膜和皮下脂肪中的BCATm和BCKD E1 α升高一致。我们的研究结果是一致的想法，组织特异性改变支链氨基酸代谢，在肝脏和脂肪组织，但不是在肌肉中，可能会导致血浆支链氨基酸在肥胖症的上升。
She P, Van Horn C, Reid T, Hutson SM, Cooney RN, Lynch CJ. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Am J Physiol Endocrinol Metab 293: E1552-E1563, 2007. First published October 9, 2007; doi: 10.1152/ajpendo.00134.2007. Elevations in branched-chain amino acids (BCAAs) in human obesity were first reported in the 1960s. Such reports are of interest because of the emerging role of BCAAs as potential regulators of satiety, leptin, glucose, cell signaling, adiposity, and body weight ( mTOR and PKC). To explore loss of catabolic capacity as a potential contributor to the obesity-related rises in BCAAs, we assessed the first two enzymatic steps, catalyzed by mitochondrial branched chain amino acid aminotransferase (BCATm) or the branched chain alpha-keto acid dehydrogenase (BCKD E1 alpha subunit) complex, in two rodent models of obesity (ob/ob mice and Zucker rats) and after surgical weight loss intervention in humans. Obese rodents exhibited hyperaminoacidemia including BCAAs. Whereas no obesity-related changes were observed in rodent skeletal muscle BCATm, pS293, or total BCKD E1 alpha or BCKD kinase, in liver BCKD E1 alpha was either unaltered or diminished by obesity, and pS293 ( associated with the inactive state of BCKD) increased, along with BCKD kinase. In epididymal fat, obesity-related declines were observed in BCATm and BCKD E1 alpha. Plasma BCAAs were diminished by an overnight fast coinciding with dissipation of the changes in adipose tissue but not in liver. BCAAs also were reduced by surgical weight loss intervention ( Roux-en-Y gastric bypass) in human subjects studied longitudinally. These changes coincided with increased BCATm and BCKD E1 alpha in omental and subcutaneous fat. Our results are consistent with the idea that tissue-specific alterations in BCAA metabolism, in liver and adipose tissue but not in muscle, may contribute to the rise in plasma BCAAs in obesity.