Abstract
BackgroundNonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis. NAFLD is mediated by changes in lipid metabolism and known risk factors include obesity, metabolic syndrome, and diabetes. The aim of this study was to better understand differences in the lipid composition of individuals with NAFLD compared to controls, by performing direct infusion lipidomics on serum biospecimens from a cohort study of adults in Mexico.MethodsA nested case-control study was conducted with a sample of 98 NAFLD cases and 100 healthy controls who are participating in an on-going, longitudinal study in Mexico. NAFLD cases were clinically confirmed using elevated liver enzyme tests and liver ultrasound or liver ultrasound elastography, after excluding alcohol abuse, and 100 controls were identified as having at least two consecutive normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (< 40 U/L) results in a 6-month period, and a normal liver ultrasound elastography result in January 2018. Samples were analyzed on the Sciex Lipidyzer Platform and quantified with normalization to serum volume. As many as 1100 lipid species can be identified using the Lipidyzer targeted multiple-reaction monitoring list. The association between serum lipids and NAFLD was investigated using analysis of covariance, random forest analysis, and by generating receiver operator characteristic (ROC) curves.ResultsNAFLD cases had differences in total amounts of serum cholesterol esters, lysophosphatidylcholines, sphingomyelins, and triacylglycerols (TAGs), however, other lipid subclasses were similar to controls. Analysis of individual TAG species revealed increased incorporation of saturated fatty acyl tails in serum of NAFLD cases. After adjusting for age, sex, body mass index, and PNPLA3 genotype, a combined panel of ten lipids predicted case or control status better than an area under the ROC curve of 0.83.ConclusionsThese preliminary results indicate that the serum lipidome differs in patients with NAFLD, compared to healthy controls, and suggest that assessing the desaturation state of TAGs or a specific lipid panel may be useful clinical tools for the diagnosis of NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis
Flores et al Lipids in Health and Disease (2021) 20:136. These preliminary results indicate that the serum lipidome differs in patients with NAFLD, compared to healthy controls, and suggest that assessing the desaturation state of TAGs or a specific lipid panel may be useful clinical tools for the diagnosis of NAFLD
NAFLD cases had higher levels of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), glucose, and TAGs compared to healthy controls
Summary
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis. Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease with an estimated global prevalence of 24% [1]. NAFLD and NASH can progress to cirrhosis and hepatocellular carcinoma (HCC) [3, 4]. Treatment options for NAFLD are limited and it has become the fastest growing cause of HCC among liver transplant candidates [5]. Predicting which individuals will progress from NAFLD to more advanced liver disease remains difficult to assess, and finding prognostic markers remains an important objective. The identification of key biomarkers that could improve the non-invasive detection of NAFLD and the development of new treatment strategies that reduce chronic liver disease incidence and mortality would be a major benefit to public health
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