Altered dietary methionine differentially impacts glutathione and methionine metabolism in long-living growth hormone-deficient Ames dwarf and wild-type mice.
Altered dietary methionine differentially impacts glutathione and methionine metabolism in long-living growth hormone-deficient Ames dwarf and wild-type mice.
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DOI：
10.1186/2046-2395-3-10
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发表时间：
2014
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影响因子：
--
通讯作者：
Rojanathammanee L
中科院分区：
文献类型：
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作者：
Brown-Borg HM;Rakoczy S;Wonderlich JA;Armstrong V;Rojanathammanee L
在各种饮食限制方案下，已经实现了延长哺乳动物的健康期和寿命。减少特定氨基酸的摄入量也被证明可以延长健康和寿命。我们最近报道，蛋氨酸（MET）限制在生长激素（GH）信号突变体的寿命延长是无效的。为了更好地理解GH在“感知”改变饮食MET中的明显必要性，本研究旨在评价长期生长激素缺乏艾姆斯侏儒和野生型小鼠在限制（0.16%）、低（0.43%）或丰富（1.3%）饮食MET摄入8周后的MET和谷胱甘肽（GSH）代谢（以及其他途径）。在肝组织中检查代谢物表达，而在肝、肾和肌肉组织中评价基因和蛋白质表达。在MET饮食的侏儒小鼠中保持体重，而在较高水平的MET的野生型小鼠中体重增加。艾姆斯小鼠的肝脏MET水平相似，而无论饮食MET摄入量如何，几种MET途径酶均升高。在艾姆斯小鼠中转硫酶也升高，但半胱氨酸水平的差异在基因型之间没有差异。与野生型小鼠相比，侏儒小鼠在MET限制下保持较高水平的GSH，而在硫氧还蛋白和谷氧还蛋白中也检测到基因型和饮食效应。MET限制增加了两种基因型中的转甲基化，如增加的S-腺苷甲硫氨酸（SAM）、甜菜碱和二甲基甘氨酸所示。饮食不影响糖酵解成分的水平，但侏儒小鼠表现出更高水平的这一途径的关键成员。辅酶A和脂肪酸氧化的措施升高侏儒小鼠和饮食的影响。艾姆斯和野生型小鼠之间的这种成分分析表明，观察到的寿命差异可能是由非典型MET代谢和对多个系统的下游影响造成的。对不同饮食的反应性的总体缺乏在侏儒小鼠的许多代谢途径中得到很好的反映，表明GH信号传导在区分饮食氨基酸水平的能力中的重要性。本文的在线版本（doi：10.1186/2046-2395-3-10）包含补充材料，可供授权用户使用。
Extending mammalian health span and life span has been achieved under a variety of dietary restriction protocols. Reducing the intake of a specific amino acid has also been shown to extend health and longevity. We recently reported that methionine (MET) restriction is not effective in life span extension in growth hormone (GH) signaling mutants. To better understand the apparent necessity of GH in the ‘sensing’ of altered dietary MET, the current study was designed to evaluate MET and glutathione (GSH) metabolism (as well as other pathways) in long-living GH-deficient Ames dwarf and wild-type mice following 8 weeks of restricted (0.16%), low (0.43%), or enriched (1.3%) dietary MET consumption. Metabolite expression was examined in liver tissue, while gene and protein expression were evaluated in liver, kidney, and muscle tissues. Body weight was maintained in dwarf mice on the MET diets, while wild-type mice on higher levels of MET gained weight. Liver MET levels were similar in Ames mice, while several MET pathway enzymes were elevated regardless of dietary MET intake. Transsulfuration enzymes were also elevated in Ames mice but differences in cysteine levels were not different between genotypes. Dwarf mice maintained higher levels of GSH on MET restriction compared to wild-type mice, while genotype and diet effects were also detected in thioredoxin and glutaredoxin. MET restriction increased transmethylation in both genotypes as indicated by increased S-adenosylmethionine (SAM), betaine, and dimethylglycine. Diet did not impact levels of glycolytic components, but dwarf mice exhibited higher levels of key members of this pathway. Coenzyme A and measures of fatty acid oxidation were elevated in dwarf mice and unaffected by diet. This component analysis between Ames and wild-type mice suggests that the life span differences observed may result from the atypical MET metabolism and downstream effects on multiple systems. The overall lack of responsiveness to the different diets is well reflected across many metabolic pathways in dwarf mice indicating the importance of GH signaling in the ability to discriminate dietary amino acid levels. The online version of this article (doi:10.1186/2046-2395-3-10) contains supplementary material, which is available to authorized users.