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高脂饮食喂养诱导的小鼠肩胛间棕色脂肪和皮下白色脂肪组织的整合蛋白质组和磷酸化蛋白质组分析。

Integrated proteome and phosphoproteome analysis of interscapular brown adipose and subcutaneous white adipose tissues upon high fat diet feeding in mouse.

机构信息

School of Bioengineering, East China University of Science and Technology, Shanghai 200237, China; CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Surgical Critical Care Medicine, Zhongshan Hospital Xuhui Branch, Fudan University, China.

出版信息

J Proteomics. 2022 Mar 20;255:104500. doi: 10.1016/j.jprot.2022.104500. Epub 2022 Jan 29.

Abstract

Thermogenesis is a promising approach to limit weight gain in response to excess nutrition. In contrast to cold-induced thermogenesis, the molecular and cellular mechanisms of diet-induced thermogenesis (DIT) have not been fully characterized. Here, we explored the response of brown adipose tissue (BAT) and subcutaneous white adipose tissue (sWAT) to high fat diet (HFD) using proteome and phosphoproteome analysis. We observed that after HFD, Uncoupling protein 1 (UCP1) and its phosphorylation were only increased in BAT. Furthermore, proteins involved in fatty acid oxidation, tricarboxylic acid cycle, and oxidative phosphorylation were also upregulated in BAT. Nevertheless, most metabolic related proteins were downregulated in sWAT. We found that these metabolic changes accompanied with different variation of mitochondrial proteins between BAT and sWAT. After HFD, most mitochondrial proteins were decreased in sWAT, but not in BAT. This effect was correlated with decreased mitochondrial ribosomal proteins in sWAT. Finally, through phosphoproteomic analysis, we predicted the activities of kinases in HFD mice and observed that there were more kinases inactivated in sWAT. Finally, this dataset provides a valuable resource for molecular researchers in the fields of obesity and obesity-related disease. SIGNIFICANCE: Thermogenesis is a promising approach to combat obesity in response to excess energy. Nevertheless, the molecular and cellular mechanisms of DIT have not been fully characterized. Herein, we employed mass spectrometry (MS)-based proteomics and phosphoproteomics to identify differentially regulated proteins and phosphosites in BAT and sWAT of mice fed with HFD. This study unveils the differential regulatory networks of HFD in BAT and sWAT, which provides reference omics data to future researchers.

摘要

产热是限制过量营养导致体重增加的一种有前途的方法。与冷诱导产热相反,饮食诱导产热(DIT)的分子和细胞机制尚未完全阐明。在这里,我们使用蛋白质组和磷酸蛋白质组分析来研究棕色脂肪组织(BAT)和皮下白色脂肪组织(sWAT)对高脂肪饮食(HFD)的反应。我们观察到,在用 HFD 处理后,解偶联蛋白 1(UCP1)及其磷酸化仅在 BAT 中增加。此外,脂肪酸氧化、三羧酸循环和氧化磷酸化相关的蛋白质也在 BAT 中上调。然而,大多数代谢相关蛋白在 sWAT 中下调。我们发现这些代谢变化伴随着 BAT 和 sWAT 之间线粒体蛋白的不同变化。在用 HFD 处理后,大多数线粒体蛋白在 sWAT 中减少,但在 BAT 中没有。这种效应与 sWAT 中线粒体核糖体蛋白的减少有关。最后,通过磷酸蛋白质组分析,我们预测了 HFD 小鼠中激酶的活性,并观察到 sWAT 中有更多的激酶失活。最后,这个数据集为肥胖和肥胖相关疾病领域的分子研究人员提供了有价值的资源。意义:产热是一种有前途的方法,可以在应对多余的能量时对抗肥胖。然而,DIT 的分子和细胞机制尚未完全阐明。在此,我们使用基于质谱(MS)的蛋白质组学和磷酸蛋白质组学来鉴定 HFD 喂养的小鼠 BAT 和 sWAT 中差异调节的蛋白质和磷酸化位点。这项研究揭示了 HFD 在 BAT 和 sWAT 中的差异调节网络,为未来的研究人员提供了参考组学数据。

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