Nagarajan Shilpa R, Brandon Amanda E, McKenna Jessie A, Shtein Harrison C, Nguyen Thinh Q, Suryana Eurwin, Poronnik Philip, Cooney Gregory J, Saunders Darren N, Hoy Andrew J
Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
PLoS One. 2017 Mar 22;12(3):e0174431. doi: 10.1371/journal.pone.0174431. eCollection 2017.
Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced insulin resistance. We identified 1267 ubiquitinated proteins in rat liver across diet and insulin-stimulated conditions, with 882 proteins common to all conditions. KEGG pathway analysis of these proteins identified enrichment of metabolic pathways, TCA cycle, glycolysis/gluconeogenesis, fatty acid metabolism, and carbon metabolism, with similar pathways altered by diet and insulin resistance. Thus, the rat liver ubiquitome is sensitive to diet and insulin stimulation and this is perturbed in insulin resistance.
泛素是一种关键的翻译后修饰，可调节众多细胞过程，但其在代谢性疾病中的作用尚未得到充分表征。在本研究中，我们鉴定了大鼠肝脏中的体内泛素化蛋白质组，并确定了在急性胰岛素刺激以及高脂和高蔗糖饮食诱导的胰岛素抵抗情况下该泛素化蛋白质组的变化。我们在不同饮食和胰岛素刺激条件下的大鼠肝脏中鉴定出1267种泛素化蛋白，其中882种蛋白在所有条件下均存在。对这些蛋白进行的KEGG通路分析表明，代谢通路、三羧酸循环、糖酵解/糖异生、脂肪酸代谢和碳代谢均有富集，饮食和胰岛素抵抗会改变相似的通路。因此，大鼠肝脏泛素化蛋白质组对饮食和胰岛素刺激敏感，且在胰岛素抵抗状态下会受到干扰。
