瘦型非酒精性脂肪性肝病的临床特征及血清脂质组学研究

肝脏 ›› 2023, Vol. 28 ›› Issue (7): 799-805.

瘦型非酒精性脂肪性肝病的临床特征及血清脂质组学研究

张思敏, 杜晟楠, 袁乙富, 何诗嘉, 曹勤, 蒋元烨

200062 上海中医药大学附属普陀医院教育规培科(张思敏),上海中医药大学附属普陀医院消化内科(杜晟楠,袁乙富,何诗嘉,曹勤,蒋元烨)

收稿日期:2023-01-20 发布日期:2023-09-19
通讯作者: 蒋元烨, Email:yuanye1014@126.com
基金资助:
上海市自然科学基金(22ZR1455900);上海市普陀区卫生健康系统科技创新项目重点项目(ptkwws202201);上海中医药大学后备卓越中医人才项目(20D-RC-02);上海市名中医沈红权传承工作室(ptzygzs2201,HGZS-202224);上海市普陀区杏林优青人才培养计划(ptxlyq2201);上海市普陀区卫生健康系统特色专病建设项目(2023tszb01)

The clinical characterization and serum lipidomic analysis of lean nonalcoholic fatty liver disease

ZHANG Si-min¹, DU Shen-nan², YUAN Yi-fu², HE Shi-jia², CAO Qin², JIANG Yuan-ye

1. Education Planning Department of Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China;
2. Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China

Received:2023-01-20 Published:2023-09-19
Contact: JIANG Yuan-ye, Email:yuanye1014@126.com

摘要/Abstract

摘要： 目的比较瘦型非酒精性脂肪性肝病(NAFLD)患者与瘦型健康人群的临床数据和血清脂质差异。方法收集瘦型NAFLD患者57例以及瘦型健康对照50例。记录所有受试者的临床信息以及血液生化指标数据,应用超高效液相色谱-高分辨静电场轨道阱质谱(UPLC-Orbitrap MS)进行血清脂质组学分析;使用主成分分析法(PCA)和正交偏最小二乘法判别分析(OPLS-DA)对脂质组学数据进行多元统计分析。结果两组之间性别差异有统计学意义(P<0.05);瘦型NAFLD组BMI显著高于瘦型对照组(P<0.01)。瘦型NAFLD组WBC、RBC、HGB、HCT、肌酐、尿酸、γ-GT、ALT、TG分别为(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显著高于对照组(P<0.05),而瘦型NAFLD组的HDL、APOA1分别为1.27(1.10,1.52)μmol/L、1.39(1.26,1.57)g/L显著低于对照组(P<0.05)。脂质组学结果显示两组之间脂质代谢具有明显差异,共鉴定到差异性脂质(VIP值>1、P<0.05且两组间含量差异倍数FC > 1.5)570种,主要为磷脂酰胆碱(PC)、三酰甘油(TG)、鞘磷脂(SM)、溶血磷脂酰胆碱(LPC)、磷脂酰乙醇胺(PE)、双甘脂(DG)、溶血磷脂酰乙醇胺(LPE)、神经酰胺(Cer)。与对照组相比,瘦型NAFLD组血清脂质大多数呈上调趋势;在呈下调趋势的脂质中,主要为SM(22种)和PC(22种)。结论与瘦型健康人群相比,瘦型NAFLD患者可能存在代谢异常、肝功能受损、胰岛素抵抗。

关键词: 非酒精性脂肪性肝病, 瘦型, 非肥胖, 脂质组学

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

张思敏, 杜晟楠, 袁乙富, 何诗嘉, 曹勤, 蒋元烨. 瘦型非酒精性脂肪性肝病的临床特征及血清脂质组学研究[J]. 肝脏, 2023, 28(7): 799-805.

ZHANG Si-min, DU Shen-nan, YUAN Yi-fu, HE Shi-jia, CAO Qin, JIANG Yuan-ye. The clinical characterization and serum lipidomic analysis of lean nonalcoholic fatty liver disease[J]. Chinese Hepatolgy, 2023, 28(7): 799-805.

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