Lipidomics in Nonalcoholic Fatty Liver Disease
Laura G. Draijer, Denise Froon‐Torenstra, Michel van Weeghel, Frédéric M. Vaz, Anneloes E. Bohte, Adriaan G. Holleboom, Marc A. Benninga, Bart G.P. Koot
Abstract
OBJECTIVES: Disturbances in lipid metabolism play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Using lipidomics, an analytical technique that is used to broadly survey lipid metabolism, we searched for biomarkers in plasma that are correlated with the presence of hepatic steatosis in children with obesity. METHODS: Lipidomics was performed in plasma samples of 21 children with obesity in whom steatosis was detected using proton magnetic resonance spectroscopy (H-MRS) and were compared with the lipidome of 21 samples of nonsteatotic subjects with obesity. RESULTS: Forty-two samples were analyzed (57% boys; median age 15 years). A total of 18 lipid classes constituting 839 different lipid species were identified. A statistically significant increase in alkyldiacylglycerol (TG[O]) and phosphatidylethanolamine (PE) species and a significant decrease in alkyl/alkenyl-phosphatidylethanolamine (PE[O]), alkyl/alkenyl-lysophosphatidylethanolamine (LPE[O]) and alkyl/alkenyl-phosphatidylcholine (PC[O]) was observed in children with hepatic steatosis compared with controls. Twelve individual lipid species of 3 lipid classes were significantly increased in steatotic subjects compared with controls. CONCLUSIONS: In this pilot study, we found statistically significant alterations in 5 major lipid classes and 12 individual lipid species in children with steatosis. These might be potential biomarkers for pediatric NAFLD. Lipidomic studies in larger cohorts of children are needed to determine the diagnostic value of these lipids and determine whether results can be generalized for different age groups and ethnic backgrounds.