Leucine and protein metabolism in obese Zucker rats.
Leucine and protein metabolism in obese Zucker rats.
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DOI：
10.1371/journal.pone.0059443
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lynch CJ
中科院分区：
文献类型：
--
作者：
She P;Olson KC;Kadota Y;Inukai A;Shimomura Y;Hoppel CL;Adams SH;Kawamata Y;Matsumoto H;Sakai R;Lang CH;Lynch CJ
支链氨基酸(BCAA)是蛋白质积累的循环营养信号，然而，它们在肥胖和升高似乎是糖尿病的预后。为了了解肥胖影响支链氨基酸和蛋白质代谢的机制，我们利用代谢组学方法，测量了[1-14C]-亮氨酸代谢率、组织特异性蛋白质合成和支链酮酸脱氢酶复合体(BCKDC)的活性。体重增加(53%)，肝脏增加(107%)，脂肪增加(∼300%)，但足底和腓肠肌重量减少(−21-24%)。肥胖大鼠血浆BCAA和BCKA分别升高45-69%和∼100%。促进这些上升的过程似乎包括增加饮食摄入量(23%)，亮氨酸(Leu)周转和蛋白质分解[每克脱脂体重(Ffm)35%，尿蛋白分解标志物：3-甲基组氨酸(183%)和4-羟基脯氨酸(766%)]，以及每克肾脏、心脏、腓肠肌和肝脏的BCKDC减少(−47-66%)。全身(FFM校正)、腓肠肌和肝脏的肥胖使循环中支链氨基酸的一个处理过程-蛋白质合成增加了23%-29%。尽管观察到BCKDC每转基因组织的活性下降，但肥胖大鼠全身亮氨酸氧化率分别高出22%和59%，归一化为体重和FFM。8种由支链氨基酸分解代谢衍生的酰基肉碱的尿液浓度也持续升高。BCAA氧化的意外增加可能是由于肝脏中的底物效应。支持这一观点的是，与其他组织相比，BCKA在肝脏中的升高(193-418%)高于血浆或肌肉，肝脏BCKDC活性的每克损失完全被肝脏质量的增加所抵消。综上所述，我们的结果表明，血浆BCKA可能比BCAA代表更敏感的肥胖代谢标志。支持肥胖Zucker大鼠BCKA升高的过程包括增加膳食摄入量、亮氨酸和蛋白质周转以及BCKDC活性受损。支链氨基酸/支链氨基酸比值升高可能是蛋白质合成和支链氨基酸氧化水平升高的原因之一。
Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-14C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA) dehydrogenase complex (BCKDC) activities. Male obese Zucker rats (11-weeks old) had increased body weight (BW, 53%), liver (107%) and fat (∼300%), but lower plantaris and gastrocnemius masses (−21–24%). Plasma BCAAs and BCKAs were elevated 45–69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%), leucine (Leu) turnover and proteolysis [35% per g fat free mass (FFM), urinary markers of proteolysis: 3-methylhistidine (183%) and 4-hydroxyproline (766%)] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (−47–66%). A process disposing of circulating BCAAs, protein synthesis, was increased 23–29% by obesity in whole-body (FFM corrected), gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193–418%) than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein turnover along with impaired BCKDC activity. Elevated BCAAs/BCKAs may contribute to observed elevations in protein synthesis and BCAA oxidation.
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影响因子：
56.9
作者：
Cota, D;Proulx, K;Seeley, RJ
通讯作者：
Seeley, RJ
影响因子：
4.3
作者：
Deo, Rahul C.;Hunter, Luke;Roth, Frederick P.
通讯作者：
Roth, Frederick P.
影响因子：
6.5
作者：
Buque, Xabier;Jose Martinez, Maria;Ochoa, Begona
通讯作者：
Ochoa, Begona
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
6.9
作者：
De Vogel-van den Bosch, Johan;Hoeks, Joris;Schrauwen, Patrick
通讯作者：
Schrauwen, Patrick