The Effects of Graded Levels of Calorie Restriction: XIV. Global Metabolomics Screen Reveals Brown Adipose Tissue Changes in Amino Acids, Catecholamines, and Antioxidants After Short-Term Restriction in C57BL/6 Mice.

The Effects of Graded Levels of Calorie Restriction: XIV. Global Metabolomics Screen Reveals Brown Adipose Tissue Changes in Amino Acids, Catecholamines, and Antioxidants After Short-Term Restriction in C57BL/6 Mice.
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DOI:
10.1093/gerona/glz023
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发表时间:
2020-01-20
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;Mitchell SE;Derous D;Wang Y;Chen L;Han JJ;Promislow DEL;Lusseau D;Douglas A;Speakman JR

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进行热量限制(CR)的动物通常会降低体温以节省能量。当需要快速产热时,棕色脂肪组织(BAT)通过去甲肾上腺素刺激,因为它由于电子传递链与ATP合成的解偶联而具有高度代谢活性。为了更好地了解BAT代谢如何随着CR而变化,我们使用代谢组学来鉴定883种代谢物,这些代谢物在C57 BL/6小鼠的BAT中显著差异表达,与每天自由进食(AL)12小时的小鼠相比,喂食分级CR(相对于其个体基线摄入量的10%,20%,30%和40% CR)。通路分析显示,分级CR对TCA循环和脂肪酸降解有影响。此外,在BAT代谢组中,随着CR分级,核酸和儿茶酚胺途径增加。我们看到CR的抗氧化剂增加,表明线粒体解偶联的有益作用。重要的是,BAT激活的引发剂去甲肾上腺素随着CR增加,而其前体l-酪氨酸和多巴胺减少,表明代谢物通过激活途径转移。其中几个关键变化与食物预期活动和体温相关,表明BAT激活可能是由对饥饿的反应驱动的。
Animals undergoing calorie restriction (CR) often lower their body temperature to conserve energy. Brown adipose tissue (BAT) is stimulated through norepinephrine when rapid heat production is needed, as it is highly metabolically active due to the uncoupling of the electron transport chain from ATP synthesis. To better understand how BAT metabolism changes with CR, we used metabolomics to identify 883 metabolites that were significantly differentially expressed in the BAT of C57BL/6 mice, fed graded CR (10%, 20%, 30%, and 40% CR relative to their individual baseline intake), compared with mice fed ad libitum (AL) for 12 hours a day. Pathway analysis revealed that graded CR had an impact on the TCA cycle and fatty acid degradation. In addition, an increase in nucleic acids and catecholamine pathways was seen with graded CR in the BAT metabolome. We saw increases in antioxidants with CR, suggesting a beneficial effect of mitochondrial uncoupling. Importantly, the instigator of BAT activation, norepinephrine, was increased with CR, whereas its precursors l-tyrosine and dopamine were decreased, indicating a shift of metabolites through the activation pathway. Several of these key changes were correlated with food anticipatory activity and body temperature, indicating BAT activation may be driven by responses to hunger.
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