Responses of the Serum Lipid Profile to Exercise and Diet Interventions in Nonalcoholic Fatty Liver Disease

BACKGROUND: This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD). METHODS: The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry. RESULTS: After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group ( P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group ( P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group ( P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92). CONCLUSIONS: Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management.