The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57BL/6 mice.
The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57BL/6 mice.
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DOI：
10.1111/acel.12570
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发表时间：
2017-06
期刊：
影响因子：
7.8
通讯作者：
Speakman JR
中科院分区：
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
热量限制（CR）仍然是延长寿命和改善健康寿命的最有力的干预措施。使用基于全局质谱的代谢组学方法，我们确定了193种代谢物，这些代谢物在C57 BL/6小鼠的肝脏中显著差异表达（C57 BL/6小鼠），与每天自由进食12小时的小鼠相比，喂食分级水平的CR（10，20，30和40% CR）。代谢产物的差异表达也因摄食组的不同而不同。通路分析显示，分级CR对肉毒碱合成和肉毒碱穿梭通路、1-磷酸鞘氨醇（S1 P）信号传导和甲硫氨酸代谢有影响。S1 P、鞘磷脂和左旋卡尼汀与体重、瘦素、胰岛素样生长因子-1（IGF-1）和主要尿蛋白（MUP）呈负相关。此外，表现出分级效应的代谢产物，如神经酰胺、S1 P、牛磺胆酸和L-肉碱，与先前观察到的年龄相关变化呈相反方向反应。我们认为，这组代谢物的调制可能会改善肝脏的能量释放过程中涉及的脂肪酸。S1 P与过氧化氢酶活性和体温呈负相关，与食物预期活性呈正相关。给小鼠注射S1 P或S1 P受体1激动剂没有引起体温、体力活动或食物摄入量的变化，这表明这些相关性不是因果关系。
Calorie restriction (CR) remains the most robust intervention to extend lifespan and improve health span. Using a global mass spectrometry‐based metabolomic approach, we identified 193 metabolites that were significantly differentially expressed (SDE) in the livers of C57BL/6 mice, fed graded levels of CR (10, 20, 30 and 40% CR) compared to mice fed ad libitum for 12 h a day. The differential expression of metabolites also varied with the different feeding groups. Pathway analysis revealed that graded CR had an impact on carnitine synthesis and the carnitine shuttle pathway, sphingosine‐1‐phosphate (S1P) signalling and methionine metabolism. S1P, sphingomyelin and L‐carnitine were negatively correlated with body mass, leptin, insulin‐like growth factor‐ 1 (IGF‐1) and major urinary proteins (MUPs). In addition, metabolites which showed a graded effect, such as ceramide, S1P, taurocholic acid and L‐carnitine, responded in the opposite direction to previously observed age‐related changes. We suggest that the modulation of this set of metabolites may improve liver processes involved in energy release from fatty acids. S1P also negatively correlated with catalase activity and body temperature, and positively correlated with food anticipatory activity. Injecting mice with S1P or an S1P receptor 1 agonist did not precipitate changes in body temperature, physical activity or food intake suggesting that these correlations were not causal relationships.