The Effects of Graded Levels of Calorie Restriction: XIII. Global Metabolomics Screen Reveals Graded Changes in Circulating Amino Acids, Vitamins, and Bile Acids in the Plasma of C57BL/6 Mice.

The Effects of Graded Levels of Calorie Restriction: XIII. Global Metabolomics Screen Reveals Graded Changes in Circulating Amino Acids, Vitamins, and Bile Acids in the Plasma of C57BL/6 Mice.
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DOI:
10.1093/gerona/gly058
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发表时间:
2019-01-01
期刊:
The journals of gerontology. Series A, Biological sciences and medical sciences
影响因子:
--
通讯作者:
Speakman JR
Speakman JR
中科院分区:
其他
文献类型:
--
作者:
Green CL;Soltow QA;Mitchell SE;Derous D;Wang Y;Chen L;Han JJ;Promislow DEL;Lusseau D;Douglas A;Jones DP;Speakman JR

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热量限制(CR)仍然是延长寿命和改善健康的最有力的干预措施。使用基于全局质谱的代谢组学方法,我们鉴定了在C57 BL/6小鼠血浆中显著差异表达的代谢物,与每天自由进食12小时的小鼠相比,喂食分级水平的热量限制(10%CR,20%CR,30%CR和40%CR)。代谢产物的差异表达随着CR的严重程度而增加。通路分析显示,分级CR对维生素E和维生素B水平、支链氨基酸、芳香族氨基酸和脂肪酸通路有影响。大多数氨基酸与去脂质量和内脏脂肪质量呈正相关,表明与身体组成和维生素E代谢产物与胃和结肠大小相关,这可能暗示了投资于CR胃肠道器官的有益作用。此外,表现出分级效应的代谢物,如鞘氨醇、肉毒碱和胆汁酸,与我们先前对肝脏的研究相匹配,这表明CR不仅以促进能量效率的方式重塑代谢组,而且某些变化在组织中是保守的。
Calorie restriction (CR) remains the most robust intervention to extend life span and improve health span. Using a global mass spectrometry–based metabolomics approach, we identified metabolites that were significantly differentially expressed in the plasma of C57BL/6 mice, fed graded levels of calorie restriction (10% CR, 20% CR, 30% CR, and 40% CR) compared with mice fed ad libitum for 12 hours a day. The differential expression of metabolites increased with the severity of CR. Pathway analysis revealed that graded CR had an impact on vitamin E and vitamin B levels, branched chain amino acids, aromatic amino acids, and fatty acid pathways. The majority of amino acids correlated positively with fat-free mass and visceral fat mass, indicating a strong relationship with body composition and vitamin E metabolites correlated with stomach and colon size, which may allude to the beneficial effects of investing in gastrointestinal organs with CR. In addition, metabolites that showed a graded effect, such as the sphinganines, carnitines, and bile acids, match our previous study on liver, which suggests not only that CR remodels the metabolome in a way that promotes energy efficiency, but also that some changes are conserved across tissues.
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