Changes in the serum metabolomic profiles of subjects with NAFLD in response to n-3 PUFAs and phytosterol ester: a double-blind randomized controlled trial

• Published in: Food & function 2022-05, Vol.13 (9), p.5189-5201
• Main Authors: Ding, Xinwen, Xu, Yinfei, Nie, Pan, Zhong, Lingyue, Feng, Lei, Guan, Qi, Song, Lihua
• Format: Article
• Language: English
• Subjects: Arachidonic acid; Biosynthesis; Clustering; Docosahexaenoic acid; Docosahexaenoic Acids; Double-blind studies; Eicosapentaenoic Acid; Fatty acids; Fatty Acids, Omega-3; Fatty liver; Fish oils; Health risks; Humans; Lecithin; Linoleic acid; Liquid chromatography; Liver; Liver diseases; Lysophosphatidylcholine; Mass spectrometry; Mass spectroscopy; Metabolic disorders; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; Patients; Perillyl alcohol; Phosphatidylcholine; Phytosterols; Polyunsaturated fatty acids; Quadrupoles; Retinyl Esters; Serum levels; Statistical analysis; Steatosis; Supplements; Vitamin A
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/D1FO03921K

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease and threatens human health worldwide. As shown in our previous study, co-supplementation with phytosterol ester (PSE) (3.3 g day ) and n-3 polyunsaturated fatty acids (PUFAs) (450 mg eicosapentaenoic acid (EPA) + 1500 mg docosahexaenoic acid (DHA) per day) was more effective at ameliorating hepatic steatosis than treatment with PSE or n-3 PUFAs alone. In the present study, we further investigated the changes in the serum metabolic profiles of subjects with NAFLD in response to n-3 PUFAs and PSE. Thirty-one differentially altered serum metabolites were annotated using the nontargeted ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS ) analysis technique. Multivariable statistical and clustering analyses showed that co-supplementation of n-3 PUFAs and PSE was more effective at improving metabolic disorders in patients with NAFLD than treatment with n-3 PUFAs or PSE alone. The regulated metabolic pathways included metabolism of retinol, linoleic acid, arachidonic acid, glycerophospholipid, sphingolipid, and steroid hormone biosynthesis. Overall, the co-supplementation of n-3 PUFAs and PSE significantly increased the serum levels of PUFA-containing phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), perillyl alcohol and retinyl ester in patients with NAFLD after 12 weeks of intervention, and the levels of PC (14:0/20:5, 15:0/20:5), LysoPC (20:5, 22:6) and retinyl ester correlated negatively with the degree of hepatic steatosis. The regulatory effect of co-supplementation of n-3 PUFAs and PSE on metabolomic profiles may explain their potential role in alleviating hepatic steatosis in patients with NAFLD.