Caloric restriction reveals a metabolomic and lipidomic signature in liver of male mice

Abstract

Lipid composition, particularly membrane unsaturation, has been proposed as being a lifespan determinant, but it is currently unknown whether caloric restriction (CR), an accepted life-extending intervention, affects cellular lipid profiles. In this study, we employ a liquid chromatography quadrupole time-of-flight-based methodology to demonstrate that CR in the liver of male C57BL/6 mice: (i) induces marked changes in the cellular lipidome, (ii) specifically reduces levels of a phospholipid peroxidation product, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphatidylcholine, (iii) alters cellular phosphoethanolamine and triglyceride distributional profiles, (iv) affects mitochondrial electron transport chain complexes, increasing complex II and decreasing complex III and (v) is associated with specific changes in liver metabolic pathways. These data demonstrate that CR induces a specific lipidome and metabolome reprogramming event in mouse liver which is associated with lower protein oxidative damage, as assessed by mass spectrometry-based measurements. Such changes may be critical to the increased lifespan and healthspan observed in C57BL/6 mice following CR.

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

“…Previous metabolomic analyses on the livers of C57BL/6 CR mice suggest that glycolysis, fatty acid oxidation and amino acid pathways are significantly altered (Collino et al ., 2013; Fok et al ., 2014; Jové et al ., 2014). These changes were consistent with studies that indicate metabolic reprogramming through the shift from lipogenesis to lipolysis during CR is beneficial in both male and female C57BL/6 mice (Bruss et al ., 2010; Kuhla et al ., 2014).…”

The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice

“…2014). Furthermore, a recent lipidomic approach has demonstrated that CR significantly altered the hepatic lipidome in male C57BL/6 mice and caused a change in the relative abundance of specific triglycerides and phosphatidylethanolamines and reduced hepatic 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphatidylcholine content, a specific product of phospholipid peroxidation (Jové et al 2014). Less susceptibility of membranes to peroxidation was explained on the basis of a redistribution in the type of unsaturation: CR increased monounsaturated fatty acids (MUFA) in liver, whereas the levels of PUFA were decreased without any observed changes in saturated fatty acids (SFA).…”

“…Less susceptibility of membranes to peroxidation was explained on the basis of a redistribution in the type of unsaturation: CR increased monounsaturated fatty acids (MUFA) in liver, whereas the levels of PUFA were decreased without any observed changes in saturated fatty acids (SFA). These specific changes may be the result of a metabolic reprogramming leading to lower levels of oxidative damage which could contribute to the increased lifespan of CR mice (Jové et al 2014). …”

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

“…According to these results, we hypothesized that the extended longevity found in the CRL‐fed group correlates with the higher MUFA content in mitochondria from these animals as detected in hepatocytes and skeletal muscle (López‐Domínguez et al ., 2013, 2015b). Furthermore, the decreased susceptibility of membranes to phospholipid peroxidation may improve mitochondrial function, a phenomenon likely linked to lifespan extension (Jové et al ., 2014). …”