The impact of high-fat diet on metabolism and immune defense in small intestine mucosa.
The impact of high-fat diet on metabolism and immune defense in small intestine mucosa.
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DOI：
10.1021/pr500833v
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发表时间：
2015-01
影响因子：
4.4
通讯作者：
J. Wiśniewski;Alexandra Friedrich;T. Keller;M. Mann;H. Koepsell
中科院分区：
文献类型：
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作者：
J. Wiśniewski;Alexandra Friedrich;T. Keller;M. Mann;H. Koepsell
改进的样品制备和蛋白质组学数据分析程序使我们能够鉴定小鼠小肠粘膜中7700种不同的蛋白质，并计算>5000种蛋白质的浓度。我们比较了小鼠小肠粘膜的蛋白质浓度，这些小鼠被喂食两个月，正常饮食（ND）含有34.4%碳水化合物，19.6%蛋白质和3.3%脂肪，或高脂肪饮食（HFD）含有25.3%碳水化合物，24.1%蛋白质和34.6%脂肪。11%的定量蛋白质在ND和HFD之间存在显著差异。在HFD后，我们观察到参与蛋白质合成、蛋白质N-糖基化和囊泡运输的蛋白质升高。参与脂肪酸吸收、脂肪酸β-氧化和类固醇代谢的蛋白质也增加。糖酵解和磷酸戊糖循环酶减少，而呼吸链和ATP合成酶的蛋白质增加。位于肠上皮细胞质膜上的各种营养转运蛋白的蛋白浓度降低，包括Na（+）-d-葡萄糖协同转运蛋白SGLT 1、被动葡萄糖转运蛋白GLUT 2和H（+）-肽协同转运蛋白PEPT 1。Na（+），K（+）-ATP酶的浓度也降低，这是最强表达的肠上皮细胞转运蛋白。HFD还引起药物转运蛋白和参与药物代谢的酶的浓度变化，这表明HFD对药代动力学和毒性的影响。最后，我们观察到下调的抗体亚单位和主要组织相容性复合物II的成分，可能反映受损的免疫防御和免疫耐受HFD。我们的工作表明，小肠粘膜功能蛋白质的显着变化时，过量的脂肪消耗。
Improved procedures for sample preparation and proteomic data analysis allowed us to identify 7700 different proteins in mouse small intestinal mucosa and calculate the concentrations of >5000 proteins. We compared protein concentrations of small intestinal mucosa from mice that were fed for two months with normal diet (ND) containing 34.4% carbohydrates, 19.6% protein, and 3.3% fat or high-fat diet (HFD) containing 25.3% carbohydrates, 24.1% protein, and 34.6% fat. Eleven percent of the quantified proteins were significantly different between ND and HFD. After HFD, we observed an elevation of proteins involved in protein synthesis, protein N-glycosylation, and vesicle trafficking. Proteins engaged in fatty acid absorption, fatty acid β-oxidation, and steroid metabolism were also increased. Enzymes of glycolysis and pentose phosphate cycle were decreased, whereas proteins of the respiratory chain and of ATP synthase were increased. The protein concentrations of various nutrient transporters located in the enterocyte plasma membrane including the Na(+)-d-glucose cotransporter SGLT1, the passive glucose transporter GLUT2, and the H(+)-peptide cotransporter PEPT1 were decreased. The concentration of the Na(+),K(+)-ATPase, which turned out to be the most strongly expressed enterocyte transporter, was also decreased. HFD also induced concentration changes of drug transporters and of enzymes involved in drug metabolism, which suggests effects of HFD on pharmacokinetics and toxicities. Finally, we observed down-regulation of antibody subunits and of components of the major histocompatibility complex II that may reflect impaired immune defense and immune tolerance in HFD. Our work shows dramatic changes in functional proteins of small intestine mucosa upon excessive fat consumption.