Alloisoleucine differentiates the branched-chain aminoacidemia of Zucker and dietary obese rats.

Alloisoleucine differentiates the branched-chain aminoacidemia of Zucker and dietary obese rats.
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DOI:
10.1002/oby.20691
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发表时间:
2014-05
期刊:
影响因子:
6.9
通讯作者:
Lynch, Christopher J.
Lynch, Christopher J.
中科院分区:
医学2区
文献类型:
--
作者:
Olson, Kristine C.;Chen, Gang;Xu, Yuping;Hajnal, Andras;Lynch, Christopher J.

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循环支链氨基酸(BCAAs)在肥胖中升高,这与肥胖合并症有关。然而,目前尚不清楚肥胖是如何影响异亮氨酸的,异亮氨酸是支链酮酸脱氢酶复合物(BCKDC)疾病的一种BCAA和病理标记物。先前已经确定肥胖的Zucker大鼠在脂肪和其他组织中表现出BCKDC损伤,而DIO大鼠脂肪组织中的BCKDC损伤通过肝脏BCKDC活性增加来补偿。因此,异亮氨酸在这两种肥胖模型中被研究。从血浆中提取氨基酸并用超高效液相色谱-质谱(UPLC-MS)测定。肥胖的Zucker大鼠血浆异亮氨酸比瘦的Zucker大鼠高238%。这一升高幅度大于其他BCAAs(107-124%)。DIO大鼠的异亮氨酸没有显著变化,尽管其他支链氨基酸升高(15-66%)。异亮氨酸在肥胖的Zucker而不是DIO大鼠中升高,这与Zucker而不是DIO大鼠中已知的BCKDC整体损伤一致。细胞毒性支链酮酸(BCKAs)在影响BCKDC的遗传疾病中积累。BCKAs增加活性氧、应激激酶激活和线粒体功能障碍。由于这些因素是肥胖合并症的基础,因此鉴别异亮氨酸升高的肥胖个体可能很重要。
Circulating branched-chain amino acids (BCAAs) are elevated in obesity and this has been linked to obesity comorbidities. However it is unclear how obesity affects alloisoleucine, a BCAA and pathognomonic marker of branched-chain keto acid dehydrogenase complex (BCKDC) disorders. It has been previously established that obese Zucker rats exhibit BCKDC impairments in fat and other tissues, whereas BCKDC impairments in adipose tissue of DIO rats are compensated by increased hepatic BCKDC activity. Therefore, alloisoleucine was investigated in these two obesity models. Amino acids were extracted from plasma and measured using ultra performance liquid chromatography mass spectrometry (UPLC-MS). Plasma alloisoleucine was 238% higher in obese compared to lean Zucker rats. This elevation was greater than that of other BCAAs (107–124%). DIO rats had no significant change in alloisoleucine, despite elevations in other BCAAs (15–66%). Alloisoleucine was elevated in obese Zucker but not DIO rats consistent with known global impairments of BCKDC in Zucker but not DIO rats. Cytotoxic branched-chain ketoacids (BCKAs) accumulate in genetic disorders affecting BCKDC. BCKAs increase reactive oxygen species, stress kinase activation and mitochondrial dysfunction. Inasmuch as these factors underlie obesity comorbidities, it may important to identify obese individuals with elevated alloisoleucine.
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