With the development of modern mass spectrometers (MS) coupled to

With the development of modern mass spectrometers (MS) coupled to highly efficient liquid chromatography (LC) systems, it is now possible to measure thousands of metabolites, mainly lipids, in as little as

a few minutes per sample. LC/MS is particularly well-suited to identify novel NAFLD biomarkers, where lipid metabolic changes and the Selleck RO4929097 lipotoxicity they generate are thought to play a key function in disease development and progression. Recent awareness that each category of lipid consists of thousands of molecular species emphasizes the need to search for individual lipid molecules in addition to measuring total changes in the concentration of fatty acids, glycerophospholipids, diacylglycerols, TAG, and bile acids. Our group has recently shown the potential of such an approach in describing common serum metabolic alterations observed in a gene knockout animal NAFLD model and a small cohort of morbidly obese patients with NAFLD, who are closely matched in clinical features such as sex, age, and BMI.12 Others have used CB-839 mouse similar techniques to describe a series

of metabolite biomarkers found in the serum and liver tissue of patients with NAFLD who have a variety of clinocopathological characteristics.13 More recently, we studied the serum lipidomics and amino acid profile, as a function of BMI, in about 500 biopsied individuals with normal liver, or who had been diagnosed with steatosis or NASH. This study has identified a BMI-dependent metabolic signature able to reliably distinguish NASH from steatosis, showing an AUROC of 0.85 (Barr J, Lu SC, Mato JM, unpublished data). This list of novel BMI-dependent biomarkers is made 上海皓元 of individual molecular species belonging to different lipid categories (i.e., eicosanoids, nonesterified fatty acids,

glycerophospholipids, sphingomyelins, ceramides, diacylglycerols, and TAG). The goal of this metabolomics-based approach is to develop perfect (99%-100% sensitivity and specificity) noninvasive diagnostic tests for liver steatosis, NASH, and fibrosis by combining the tried and trusted old biomarkers with these new lipid biomarkers. These tests should also be responsive to changes in NAFLD severity due to therapeutic intervention and time. This task is not suited for every laboratory, because extreme care needs to be taken to ensure that the analytical methods used are well validated and the new specific biomarkers correctly identified.

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