Large-scaled human serum sphingolipid profiling by using reversed-phase liquid chromatography coupled with dynamic multiple reaction monitoring of mass spectrometry: Method development and application in hepatocellular carcinoma

Li, Jia; Hu, Chunxiu; Zhao, Xinjie; Dai, Weidong; Chen, Shili; Xu, Guowang

doi:10.1016/j.chroma.2013.10.064

Cited by 39 publications

(28 citation statements)

References 42 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CER is produced by hydrolysis of SM and synthesized from serine and palmitoyl-CoA [50]. CERs are typically found at trace levels in tissues [51, 52]. Hence, CER may fail to be screened out as metabolite markers using statistical methods.…”

Section: Resultsmentioning

confidence: 99%

Bile acid signaling in lipid metabolism: Metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice

Jiang

Cheng

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

164

View full text Add to dashboard Cite

Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway in the liver and plays an important role in regulating lipid, glucose and energy metabolism. Transgenic mice overexpressing CYP7A1 (CYP7A1-tg mice) were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and diabetes. However the mechanism of resistance to HFD-induced obesity of CYP7A1-tg mice has not been determined. In this study, metabolomic and lipidomic profiles of CYP7A1-tg mice were analyzed to explore the metabolic alterations in CYP7A1-tg mice that govern the protection against obesity and insulin resistance by using ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry combined with multivariate analyses. Lipidomics analysis identified seven lipid markers including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides that were significantly decreased in serum of HFD-fed CYP7A1-tg mice. Metabolomics analysis identified 13 metabolites in bile acid synthesis including taurochenodeoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, taurocholic acid, and tauro-β-muricholic acid (T-β-MCA) that differed between CYP7A1-tg and wild-type mice. Notably, T-β-MCA, an antagonist of the farnesoid X receptor (FXR) was significantly increased in intestine of CYP7A1-tg mice. This study suggests that reducing 12α-hydroxylated bile acids and increasing intestinal T-β-MCA may reduce high fat diet-induced increase of phospholipids, sphingomyelins and ceramides, and ameliorate diabetes and obesity.

show abstract

Section: Resultsmentioning

confidence: 99%

Bile acid signaling in lipid metabolism: Metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice

Jiang

Cheng

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

164

View full text Add to dashboard Cite

show abstract

“…Both SM and CER are bioactive sphingolipids implicated in modulating various cellular events, including proliferation, differentiation, apoptosis, and inflammation (16). SM concentrations are relatively low and CER are typically found at trace levels in tissues (18,26), and thus they may be missed as metabolite markers using statistical methods. Therefore, to determine the level trends of SM and CER in various groups, a set of SM and CER metabolites were quantitated using UPLC-MS/MS.…”

Section: Role Of Ppar␣ Activation In Experimental Colitismentioning

confidence: 99%

PPARα-dependent exacerbation of experimental colitis by the hypolipidemic drug fenofibrate

Jiang

Tanaka

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Fibrates, such as fenofibrate, are peroxisome proliferator-activated receptor-α (PPARα) agonists and have been used for several decades as hypolipidemic agents in the clinic. However, contradictory observations exist on the role of fibrates in host response to acute inflammation, with unclear mechanisms. The role of PPARα in colitis was assessed using fenofibrate and Ppara-null mice. Wild-type or Ppara-null mice were subjected to acute colitis under three distinct protocols, dextran sulfate sodium, trinitrobenzenesulfonic acid, and Salmonella Typhi. Serum and colon lipidomics were analyzed to characterize the metabolic profiles by ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Messenger RNAs of PPARα target genes and genes involved in inflammation were determined by qunatitative PCR analysis. Fenofibrate treatment exacerbated inflammation and tissue injury in acute colitis, and this was dependent on PPARα activation. Lipidomics analysis revealed that bioactive sphingolipids, including sphingomyelins (SM) and ceramides, were significantly increased in the colitis group compared with the control group; this was further potentiated following fenofibrate treatment. In the colon, fenofibrate did not reduce the markedly increased expression of mRNA encoding TNFα found in the acute colitis model, while it decreased hydrolysis and increased synthesis of SM, upregulated RIPK3-dependent necrosis, and elevated mitochondrial fatty acid β-oxidation, which were possibly related to the exacerbated colitis.

show abstract

“…In the sera and plasma of HCC patients, SMs were decreased [29,30], as well as in the present study, which might attribute to the deactivation of SM synthases [40]. Besides, up-regulation of LacCer was also observed in HCC patients from another study [41]. However, the relationship between GalCer and HCC is few till now, which needs further investigation in the future.…”

Section: Altered Lipid Species Associated With Hccmentioning

confidence: 58%

Plasma Lipidomic Analysis to Identify Novel Biomarkers for Hepatocellular Carcinoma

Yang

Bai²,

Han

et al. 2017

J. Anal. Test.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) accounts for the major primary liver cancer, and its morbidity and mortality rates are very high. Identification of novel biomarkers for the early diagnosis and treatment of this disease is of crucial importance. In this study, a continuous-flow normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF/MS) method was used to detect lipid species in human plasma from HCC patients and healthy controls. As a result, the two groups were clearly separated by principal component analysis. Besides, 23 lipid species with corrected p value \0.05 and fold change [1.5 were proposed as potential lipid biomarkers for HCC. Among them, 9 lipid species, including galactosylceramide (36:5), free fatty acid (20:4), phosphatidylethanolamine (40:6), phosphatidylethanolamine (38:6), diacylglycerol (40:5), diacylglycerol (44:2), lactosylceramide (40:3), phosphatidylcholine (40:6), and free fatty acid (22:5), exhibited excellent ability to distinguish HCC patients from healthy controls with the area under the receiver-operating characteristic curve [0.900, showing promising clinical value. Taken together, these results indicate the great potential of NP/RP 2D LC-QToF/MS method in disease diagnosis, which might be helpful in clinical practice.

show abstract

Large-scaled human serum sphingolipid profiling by using reversed-phase liquid chromatography coupled with dynamic multiple reaction monitoring of mass spectrometry: Method development and application in hepatocellular carcinoma

Cited by 39 publications

References 42 publications

Bile acid signaling in lipid metabolism: Metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice

Bile acid signaling in lipid metabolism: Metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice

PPARα-dependent exacerbation of experimental colitis by the hypolipidemic drug fenofibrate

Plasma Lipidomic Analysis to Identify Novel Biomarkers for Hepatocellular Carcinoma

Contact Info

Product

Resources

About