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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 Journals of Gerontology Series A: Biological Sciences and Medical Sciences ( IF 5.1 ) Pub Date : 2020-01-20 , DOI: 10.1093/gerona/glz023
Cara L Green 1 , Sharon E Mitchell 1 , Davina Derous 1 , Yingchun Wang 2 , Luonan Chen 3 , Jing-Dong J Han 4 , Daniel E L Promislow 5 , David Lusseau 1 , Alex Douglas 1 , John R Speakman 1, 2
Affiliation  

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.

中文翻译:

热量限制分级的影响:XIV。全球代谢组学筛选揭示了 C57BL/6 小鼠短期限制后棕色脂肪组织中氨基酸、儿茶酚胺和抗氧化剂的变化。

接受热量限制 (CR) 的动物通常会降低体温以节省能量。当需要快速产生热量时,棕色脂肪组织 (BAT) 会受到去甲肾上腺素的刺激,因为由于 ATP 合成中电子传递链的解偶联,棕色脂肪组织具有高度代谢活性。为了更好地了解 BAT 代谢如何随 CR 变化,我们使用代谢组学鉴定了 883 种代谢物,这些代谢物在喂食分级 CR(10%、20%、30% 和 40% CR)的 C57BL/6 小鼠的 BAT 中表达显着差异。与每天 12 小时随意进食 (AL) 的小鼠相比。通路分析显示分级 CR 对 TCA 循环和脂肪酸降解有影响。此外,随着 BAT 代谢组中分级 CR 的增加,核酸和儿茶酚胺途径也有所增加。我们看到 CR 导致抗氧化剂增加,这表明线粒体解偶联具有有益作用。重要的是,BAT 激活的引发剂去甲肾上腺素随着 CR 的增加而增加,而其前体 L-酪氨酸和多巴胺则减少,表明代谢物通过激活途径发生了变化。其中一些关键变化与食物预期活动和体温相关,表明 BAT 激活可能是由饥饿反应驱动的。
更新日期:2020-01-21
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