Abstract
Background Limited prospective studies have examined changes in non-alcoholic fatty-liver disease (NAFLD) related serum-metabolites and none the effects of NAFLD-reversion. We aimed to evaluate whether perturbations in metabolites indicate predisposition to NAFLD development and to assess the effects of NAFLD reversion on metabolite profiles.MethodsA targeted liquid-chromatography tandem mass-spectrometry metabolic profiling (n = 453 metabolites) approach was applied, using serum from 45 subjects of the PREDIMED study, at baseline and after a median 3.8-year follow-up. NAFLD was determined using the hepatic steatosis index; with three groups classified and studied: Group 1, not characterized as NAFLD cases during the follow-up (n = 15); Group 2, characterized as NAFLD during the follow-up (n = 15); Group 3, characterized as NAFLD-reversion during the follow-up (n = 15).ResultsAt baseline, significantly lower storage and transport lipids (triacylglycerols and cholesteryl esters), several monoetherglycerophosphocholines, acylglycerophosphocholines, ceramides and ceramide to sphingomyelin ratio (P < 0.05), were found; whereas a higher L-cystine to L-glutamate ratio (P < 0.05) was observed, in group 2 as compared to group 1.P-ether acylglycerophosphocholines, ceramides and sphingolipids were significantly different betweengroup 3 and group 1 (P < 0.05). Higher 16:1n-7 to 16:0, and 18:0 to16:0 ratio (P < 0.05), while lower 18:1n-9 to 18:0, 16:0 to 18:2n-6, and 18:3n-6 to 18:2n-6 ratio (P < 0.05) were observed in the final, compared to baseline values, in groups 2 and 3.ConclusionThe rearrangement of lipid biosynthesis and serum transport may indicate predisposition to NAFLD development. Despite an expected reduction of hepatic lipotoxicity and improved hepatic function in the participants of the study characterized as NAFLD-reversing, the side effects of NAFLD in serum metabolic profiles remained present.Trial registrationThe trial is registered at ISRCTN35739639. Registration date: 5th October 2005.
Highlights
Limited prospective studies have examined changes in non-alcoholic fatty-liver disease (NAFLD) related serum-metabolites and none the effects of NAFLD-reversion
Decreased plasma polyunsaturated fatty acids (PUFAs), as well as increased monounsaturated fatty acids (MUFAs) and eicosanoid metabolites of the lipoxygenase pathway have been reported in plasma of NAFLD patients [10]
Taking the above into account, the present study aimed to evaluate whether perturbations in serummetabolites can indicate overall predisposition to NAFLD development in participants of the PREDIMED (Prevention of Disease with Mediterranean Diet) study
Summary
Limited prospective studies have examined changes in non-alcoholic fatty-liver disease (NAFLD) related serum-metabolites and none the effects of NAFLD-reversion. Several studies focused on NAFLD association with metabolism of complex lipid classes Following this approach, Puri et al [8] reported perturbations in hepatic lipid classes, during progression from normal liver status to steatosis and NASH, as accumulation of triacyl- and diacyl-glycerols, free cholesterol, cholesterol esters and saturated fatty acids [8]. Puri et al [8] reported perturbations in hepatic lipid classes, during progression from normal liver status to steatosis and NASH, as accumulation of triacyl- and diacyl-glycerols, free cholesterol, cholesterol esters and saturated fatty acids [8] Concerning phospholipids especially, their composition appears to differentiate in the liver of patients with steatosis and NASH, with decreased concentrations of phosphatidylcholine and phosphatidylethanolamine in steatosis [8]. Decreased plasma polyunsaturated fatty acids (PUFAs), as well as increased monounsaturated fatty acids (MUFAs) and eicosanoid metabolites of the lipoxygenase pathway have been reported in plasma of NAFLD patients [10]
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