Abstract: Objective To compare the clinical features and serum lipidomic profiles between lean nonalcoholic fatty liver disease (NAFLD) patients and lean healthy subjects. Methods A total of 57 patients with lean NAFLD and 50 lean healthy controls were included in this study. The clinical information and blood biochemical indicators of all subjects were collected. The serum lipidomics was analyzed by ultra-performance liquid chromatography-Orbitrap mass spectrometry (UPLC-Orbitrap MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for multivariate statistical analysis of lipidomics data. Results The gender difference between the lean NAFLD group and the lean control group was statistically significant (P<0.05). BMI in the lean NAFLD group was significantly higher than that in the lean control group (P<0.01). Among the blood biochemical indexes, white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), creatinine, uric acid, γ-glutamyl transpeptidase (γ-GT), alanine aminotransferase (ALT) and triglyceride (TG) are (6.10±1.57)×10⁹/L, (4.51(4.34, 4.81))×10¹²/L, (137(127, 148))g/L, (41.1 (38.15, 43.7)%, (67 (57.5, 81)) μmol/L, (339.5 (298.75, 380)) μmol/L, (27 (19, 37)) U/L, (14.5 (9, 21.25)) U/L, (1.42 (0.95, 1.95)) μmol/L, respectively, which were significantly higher than those in the control group (P<0.05 or P<0.01), while HDL and APOA1 in the thin NAFLD group were (1.27 (1.10, 1.52) μmol/L, and (1.39 (1.29 6, 1.57)) g/L, which were significantly lower than those of the control group (P<0.05 or P<0.01). The results of lipomics showed that there were significant differences in lipid metabolism between the two groups. A total of 570 kinds of differential lipids were identified (VIP value>1, P<0.05) with the fold change of content difference between the two groups >1.5 (FC>1.5), mainly including phosphatidylcholine (PC), triglyceride (TG), sphingomyelin (SM), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), diglyceride (DG), lysophosphatidylethanolamine (LPE) and ceramide (Cer). Compared with the control group, most of the serum lipids in the lean NAFLD group were up-regulated; The main serum lipids with downregulated trend included 22 kinds of SM and 22 kinds of PC. Conclusion The clinical characteristics of lean NAFLD patients suggest that they may have metabolic abnormalities, impaired liver function, and insulin resistance compared with lean healthy subjects. Serum lipidomics results showed that the profile of lipid metabolism in patients with lean NAFLD was significantly different from that in lean healthy subjects. These results have reference meaning for further study of the pathogenesis of lean NAFLD and provide potential application for the diagnosis of NAFLD in lean individuals.

Key words: Nonalcoholic fatty liver disease, Lean, Nonobese, Lipidomics