SILAC-based quantitative proteomic analysis of the livers of spontaneous obese and diabetic rhesus monkeys
SILAC-based quantitative proteomic analysis of the livers of spontaneous obese and diabetic rhesus monkeys
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基于 SILAC 的自发性肥胖和糖尿病恒河猴肝脏定量蛋白质组学分析
DOI：
10.1152/ajpendo.00016.2018
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Bin Liang
中科院分区：
文献类型：
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作者：
Junlong Wang;Shimeng Xu;Jing Gao;Linqiang Zhang;Zhiguo Zhang;Wenhui Yang;Yunhai Li;Shasha Liao;Hu Zhou;Pingsheng Liu;Bin Liang
2型糖尿病（T2 DM）是一种严重的代谢紊乱，影响全球10%以上的人口。肥胖是胰岛素抵抗的主要原因，并有助于T2 DM的发展。肝脏是人体重要的代谢器官，在肥胖和糖尿病的发病机制中起着至关重要的作用。然而，肝脏在肥胖向糖尿病转变中的潜在机制尚不完全清楚。非人灵长类恒河猴是研究人类疾病的理想动物。在这里，我们首先筛选并选择了三个个体的自发性糖尿病恒河猴。有趣的是，糖尿病猴子在开始时肥胖，体重指数很高，但在一年的观察期间逐渐减轻体重。此外，我们在基于细胞培养的定量蛋白质组学中用氨基酸进行稳定同位素标记，以鉴定肥胖和糖尿病猴肝脏中表达改变的蛋白质和信号通路。总共鉴定和定量了3，509种蛋白质，其中185种蛋白质显示出改变的表达水平。基因本体分析显示，肥胖猴中参与脂肪酸β-氧化和半乳糖代谢的蛋白表达增加;糖尿病猴中参与氧化磷酸化和支链氨基酸（BCAA）降解的蛋白表达上调。此外，我们还观察到糖尿病猴肝脏中存在轻度细胞凋亡，提示糖尿病晚期出现肝损伤。综上所述，我们的肝脏蛋白质组学可能揭示了从肥胖猴的脂肪酸β-氧化到糖尿病猴的BCAA降解的独特代谢转变。
Type 2 diabetes mellitus (T2DM) is a severe metabolic disorder that affects more than 10% of the population worldwide. Obesity is a major cause of insulin resistance and contributes to the development of T2DM. Liver is an essential metabolic organ that plays crucial roles in the pathogenesis of obesity and diabetes. However, the underlying mechanisms of liver in the transition of obesity to diabetes are not fully understood. The nonhuman primate rhesus monkey is an appropriate animal for research of human diseases. Here, we first screened and selected three individuals of spontaneously diabetic rhesus monkeys. Interestingly, the diabetic monkeys were obese with a high body mass index at the beginning, but gradually lost their body weight during one year of observation. Furthermore, we performed stable isotope labeling with amino acids in cell culture-based quantitative proteomics to identify proteins and signaling pathways with altered expression in the liver of obese and diabetic monkeys. In total, 3,509 proteins were identified and quantified, of which 185 proteins displayed an altered expression level. Gene ontology analysis revealed that the expression of proteins involved in fatty acids β-oxidation and galactose metabolism was increased in obese monkeys; while proteins involved in oxidative phosphorylation and branched chain amino acid (BCAA) degradation were upregulated in diabetic monkeys. In addition, we observed mild apoptosis in the liver of diabetic monkeys, suggesting liver injury at the late onset of diabetes. Taken together, our liver proteomics may reveal a distinct metabolic transition from fatty acids β-oxidation in obese monkey to BCAA degradation in diabetic monkeys.