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Background:  There is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with perturbations in liver lipid metabolism. Liver phospholipid and fatty acid composition have been shown to be altered in NAFLD. However, detailed profiles of circulating lipids in the pathogenesis of NAFLD are lacking.    Objective:  Therefore, the objective of the present study was to examine circulating lipids and potential mechanisms related to hepatic gene expression between liver biopsy-proven simple steatosis (SS), nonalcoholic steatohepatitis (NASH) and healthy subjects.    Subjects:  Plasma phospholipid and fatty acid composition were determined in 31 healthy living liver donors as healthy controls (HC), 26 patients with simple hepatic steatosis (SS) and 20 with progressive NASH. Hepatic gene expression was analyzed by Illumina microarray in a subset of 22 HC, 16 SS and 14 NASH.    Results:  Concentrations of phosphatidylethanolamine (PE) increased relative to disease progression, HC<SS<NASH (170<210<250 μg ml −1 ), and was significantly different ( P< 0.05) between HC and NASH. Circulating phosphatidylserine (PS) and phosphatidylinositol were higher in SS and NASH compared with HC ( P< 0.05), but there was no difference between SS and NASH. Fatty acid composition of phospholipids was also remodeled. In particular, docosahexaenoic and arachidonic acid were higher ( P< 0.05) in SS and NASH relative to HC in PS. Differentially expressed hepatic genes included  ETNK1  and  PLSCR1  that are involved in PE synthesis and PS transport, respectively.    Conclusions:  The present study demonstrates that there is a disruption in phospholipid metabolism that is present in SS, but more pronounced in NASH. Intervention studies targeted at lipid metabolism could benefit SS and NASH.

Plasma phospholipids and fatty acid composition differ between liver biopsy-proven nonalcoholic fatty liver disease and healthy subjects