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饲料碳水化合物源对黄颡鱼肝组织脂代谢和 SUMOylation 修饰的影响。

Effects of dietary carbohydrate sources on lipid metabolism and SUMOylation modification in the liver tissues of yellow catfish.

机构信息

Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University,Wuhan430070, People's Republic of China.

出版信息

Br J Nutr. 2020 Dec 28;124(12):1241-1250. doi: 10.1017/S0007114520002408. Epub 2020 Jun 30.

Abstract

Dysregulation in hepatic lipid synthesis by excess dietary carbohydrate intake is often relevant with the occurrence of fatty liver; therefore, the thorough understanding of the regulation of lipid deposition and metabolism seems crucial to search for potential regulatory targets. In the present study, we examined TAG accumulation, lipid metabolism-related gene expression, the enzyme activities of lipogenesis-related enzymes, the protein levels of transcription factors or genes involving lipogenesis in the livers of yellow catfish fed five dietary carbohydrate sources, such as glucose, maize starch, sucrose, potato starch and dextrin, respectively. Generally speaking, compared with other carbohydrate sources, dietary glucose promoted TAG accumulation, up-regulated lipogenic enzyme activities and gene expressions, and down-regulated mRNA expression of genes involved in lipolysis and small ubiquitin-related modifier (SUMO) modification pathways. Further studies found that sterol regulatory element binding protein 1 (SREBP1), a key transcriptional factor relevant to lipogenic regulation, was modified by SUMO1. Mutational analyses found two important sites for SUMOylation modification (K254R and K264R) in SREBP1. Mutant SREBP lacking lysine 264 up-regulated the transactivation capacity on an SREBP-responsive promoter. Glucose reduced the SUMOylation level of SREBP1 and promoted the protein expression of SREBP1 and its target gene stearoyl-CoA desaturase 1 (SCD1), indicating that SUMOylation of SREBP1 mediated glucose-induced hepatic lipid metabolism. Our study elucidated the molecular mechanism of dietary glucose increasing hepatic lipid deposition and found that the SREBP-dependent transactivation was regulated by SUMO1 modification, which served as a new target for the transcriptional programmes governing lipid metabolism.

摘要

过量的膳食碳水化合物摄入会导致肝脏脂质合成失调,这与脂肪肝的发生密切相关。因此,深入了解脂质沉积和代谢的调控机制对于寻找潜在的调控靶点至关重要。在本研究中,我们检测了黄色鲶鱼肝脏中 TAG 积累、脂质代谢相关基因表达、与脂质生成相关酶的酶活性、参与脂质生成的转录因子或基因的蛋白质水平,这些鱼分别用五种不同的碳水化合物来源(葡萄糖、玉米淀粉、蔗糖、马铃薯淀粉和糊精)喂养。总的来说,与其他碳水化合物来源相比,膳食葡萄糖促进了 TAG 积累,上调了脂质合成酶的活性和基因表达,并下调了参与脂肪分解和小泛素相关修饰(SUMO)修饰途径的基因的 mRNA 表达。进一步的研究发现,固醇调节元件结合蛋白 1(SREBP1)是与脂质生成调节相关的关键转录因子,它被 SUMO1 修饰。突变分析发现 SREBP1 中有两个 SUMO 化修饰的重要位点(K254R 和 K264R)。缺乏赖氨酸 264 的突变 SREBP1 增强了对 SREBP 反应性启动子的转录激活能力。葡萄糖降低了 SREBP1 的 SUMO 化水平,并促进了 SREBP1 及其靶基因硬脂酰辅酶 A 去饱和酶 1(SCD1)的蛋白表达,表明 SREBP1 的 SUMO 化介导了葡萄糖诱导的肝脏脂质代谢。本研究阐明了膳食葡萄糖增加肝脏脂质沉积的分子机制,并发现 SREBP 依赖的转录激活受到 SUMO1 修饰的调节,这为调控脂质代谢的转录程序提供了一个新的靶点。

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