Abstract: To explore the mechanisms of the preventive effect of phytosterol esters (PSE) on nonalcoholic fatty liver disease (NAFLD), we investigated the effects of PSE on selected hepatic small-molecule metabolites in rats with NAFLD. A high-fat diet was used to establish a rat model of NAFLD, and PSE-fortified milk at low (0.05 g/100 g mb) and high (0.10 g/100 g mb) doses were intragastrically administered to the rats of the PSE intervention groups. Hepatic metabolite profiling of NAFLD rats was performed using ultra performance liquid chromatography tandem time-of-fight mass spectrometry (UPLC-Q-TOFMS). Using Progenesis QI v2.3 software, UNIFI data analysis platform and Metabo Analyst (http://www.metaboanalyst. ca/faces/upload/PathUploadView.xhtml), 20 differential metabolites were identified, including phosphatidic acid (PA; 16:0/20:2 (11Z, 14Z), 20:1 (11Z)/0:0); phosphatidylcholine (PC; 16:0/18:1 (11E), 18:1 (6Z)/0:0, 18:1 (9Z)/18:0, 20:3 (8Z, 11Z, 14Z)/0:0, 15:0/18:1 (11Z), 16:0/16:1 (9Z), 16:0/2:0, 17:1 (10Z)/0:0, 19:3 (10Z, 13Z, 16Z)/0:0, 20:4 (5Z, 8Z, 11Z, 14Z)/14:0)); phosphatidylethanolamine (PE; 20:3(8Z, 11Z, 14Z)/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z), 22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/17:1 (9Z)); phosphatidylglycerol (PG; 17:2 (9Z, 12Z)/22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)); sphingomyelin (SM, d18:0/16:0); glycocholic acid; and lysophosphatidylcholine (LysoPC; 18:1(9Z), 20:3 (5Z, 8Z, 11Z)), 20:3 (8Z, 11Z, 14Z)). High-dose PSE effectively regulated high-fat diet-induced glycerophospholipid metabolic pathway disorders. These results indicated that PSE could mitigate the progression of NAFLD by regulating the contents of small-molecule metabolites of phospholipids and bile acids.

Key words: phytosterol esters, liver, metabolites, nonalcoholic fatty liver, ultra performance liquid chromatography tandem with time-of-fight mass spectrometry