Yang Zhu, Yang Dianqiang, Tan Fancheng, Wong Chi Wai, Yang James Y, Zhou Da, Cai Zongwei, Lin Shu-Hai
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
Front Pharmacol. 2021 Nov 22;12:784231. doi: 10.3389/fphar.2021.784231. eCollection 2021.
The prevalence of diabetes mellitus has been increasing for decades worldwide. To develop safe and potent therapeutics, animal models contribute a lot to the studies of the mechanisms underlying its pathogenesis. Dietary induction using is a well-accepted protocol in generating insulin resistance and diabetes models. In the present study, we reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM). The other two groups of the monkeys fed with chow diet and high-fat high-sugar (HFHS) diet, respectively, were included for comparison. Analyses of various omics datasets revealed the alterations of high consistency. Between the sDM and HFHS monkeys, both the similar and unique alterations in the lipid metabolism have been demonstrated from metabolomic, transcriptomic, and proteomic data repeatedly. The comparison of the proteome and transcriptome confirmed the involvement of fatty acid binding protein 4 (FABP4) in the diet-induced pathogenesis of diabetes in macaques. Furthermore, the commonly changed genes between spontaneous diabetes and HFHS diet-induced prediabetes suggested that the alterations in the intra- and extracellular structural proteins and cell migration in the liver might mediate the HFHS diet induction of diabetes mellitus.
几十年来，全球糖尿病的患病率一直在上升。为了开发安全有效的治疗方法，动物模型对糖尿病发病机制的研究做出了巨大贡献。使用饮食诱导是生成胰岛素抵抗和糖尿病模型的一种广泛接受的方案。在本研究中，我们报告了来自以普通饮食自发发展为2型糖尿病（sDM）的猕猴的外周血和肝门静脉血的肝脏和血清的多组学分析。另外两组分别喂食普通饮食和高脂高糖（HFHS）饮食的猕猴被纳入作为对照。对各种组学数据集的分析揭示了高度一致的变化。在sDM猕猴和HFHS猕猴之间，从代谢组学、转录组学和蛋白质组学数据中反复证明了脂质代谢中既有相似的变化也有独特的变化。蛋白质组和转录组的比较证实了脂肪酸结合蛋白4（FABP4）参与猕猴饮食诱导的糖尿病发病机制。此外，自发糖尿病和HFHS饮食诱导的糖尿病前期之间共同变化的基因表明，肝脏中细胞内和细胞外结构蛋白的改变以及细胞迁移可能介导了HFHS饮食诱导的糖尿病。
