Open AccessThe effects of graded levels of calorie restriction: IX . Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57 BL /6 mice
Author(s) -
Green Cara L.,
Mitchell Sharon E.,
Derous Davina,
Wang Yingchun,
Chen Luonan,
Han JingDong J.,
Promislow Daniel E. L.,
Lusseau David,
Douglas Alex,
Speakman John R.
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12570
Subject(s) - endocrinology , medicine , biology , carnitine , calorie restriction , metabolomics , acetylcarnitine , sphingolipid , leptin , glucuronate , biochemistry , obesity , bioinformatics
Summary 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 C57 BL /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 ( MUP s). 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.