Lipidomics in non-alcoholic fatty liver disease

Table 1 Summary of main liver lipidomics studies in non-alcoholic fatty liver disease

Ref.	Tissue	Main findings in NAFLD patients compared to healthy controls	Main findings in NASH patients compared to NAFL patients
Puri et al[11], 2007	Liver	Increased: DAG, TAG, total SFA, total PUFA; stepwise increase in the mean TAG/DAG ratio, FC/PC ratio and hepatic FC from normal livers to NAFL to NASH. Decreased: Total PC in both NAFL and NASH; AA in FFA, TAG, and PC in NASH; EPA and DHA in TAG in NASH.	The n-6:n-3 FFA ratio increased in NASH
Araya et al[10], 2004	Liver, adipose tissue (fatty acid composition)	Increased: n-6:n-3 ratio, n-6 LCPUFA in liver phospholipids, total MUFA. Decreased: Long-chain PUFA of the n-6 and n-3 series in liver TAG, AA/LA ratio, EPA + DHA)/ALA in liver TAG, n-3 LCPUFA in phospholipids, total PUFA, n-3 PUFA, n-6 PUFA, AA, EPA, DHA.	The n-6:n-3 ratio increased in NASH
Allard et al[23], 2008	Liver, red blood cells (fatty acid composition)	Increased: MUFAs, palmitoleic acid (16:1 n9), and oleic acid (18:1 n9) in NASH compared to control group. Decreased: Total n-3 PUFA, long-chain n-3 (EPA + DHA) and long-chain n - 6 (AA) PUFA in NASH compared to control; RBC-FA composition similar among the three groups.	Decreased: Total n- 6-PUFA in NASH compared to NAFL
Chiappini et al[24], 2017	Liver	Increased: C14:0, C16:0, C16:1n-7, C18:1n-7, C18:1n-9, and C18:2n-6 in NASH. Decreased: Total SM, PI, PS, PE, PC in NASH.	Lipid signature of NASH (32 lipids). Decreased: AA, EPA, and DHA; total Cer.

NAFLD: Non-alcoholic fatty liver disease; NAFL: Nonalcoholic fatty liver; NASH: Nonalcoholic steatohepatitis; DAG: Diacylglycerol; TAG: Triacylglycerol; SFA: Saturated Fatty acids; PUFA: Polyunsaturated fatty acids; FC: Free cholesterol; PC: Phosphatidylcholine; FFA : Free fatty acids; LCPUFA: Long chain polyunsaturated fatty acid; MUFA: Monounsaturated fatty acid; RBC-FA: Red blood cell-fatty acids; SM: Sphingomyelin; PI: Phosphatidylinositol; PS: Phosphatidylserine; PE: Phosphatidylethanolamine; EPA: Eicosapentaenoic acid (C20:5n-3); DHA: Docosahexanoic acid (C22:6n-3); AA: Arachidonic acid (C20:4n-6); LA: Linoleic acid (C18:2n-6); ALA: α-linolenic acid (C18:3n-3); Cer: Ceramides.

Table 2 Summary of main lipidomics studies in plasma and serum in non-alcoholic fatty liver disease

Ref.	Tissue	Main findings in NAFLD patients compared to healthy control	Main findings in NASH patients compared to NAFL patients
Puri et al[26], 2009	Plasma	Increased: DAG, TAG, MUFA, dihomo-gamma-linolenic acid, palmitoleic acid, oleic acid, palmitoleic acid to palmitic acid ratio in NAFLD; stepwise increase in lipoxygenase (LOX) metabolites 5-HETE, 8-HETE, and 15-HETE from healthy controls to NAFL to NASH; 11-HETE in NASH compared with controls. Decreased: LA; total plasmalogen levels in NASH compared with controls.
Zheng et al[81], 2012	Plasma phospholipids fatty acid composition	Increased: Dihomo-gamma-linolenic acid (C20: 3n-6), total SFA in phospholipids. Decreased: Eicosanoic acid (C20: 0), cis-11-octadecenoic acid (C18: 1n-7), DHA in PL.
Loomba et al[89], 2015	plasma eicosanoid lipidomic profile	Increased: 15-HETE, 5,6-diHETrE. Decreased: 12,13-diHOME.	Increased: 11,12-diHETrE, dhk PGD2, and 20-COOH AA. Decreased:
Walle et al[80], 2016	Serum (fatty acid composition)	Increased: Palmitoleic acid in CE in individuals with NAFLD. Decreased: LA and total n-6 fatty acids in TAG in individuals with NASH.	Increased: SFA in TAG were higher in subjects with NASH, myristic acid in CE and TAG, Stearic acid in TAG. Decreased:
Tiwari-Heckler et al[27], 2018	Serum	Increased: PC and SM in NAFL and NASH. Decreased: Lysophospatidylethanolamine in NAFL and NASH individuals.	Increased: PE in patients with NASH.
Ma et al[27], 2016	Plasma	Increased: PS and PI in NAFL and NASH, DHA and AA in PS in NAFL and NASH.

NAFLD: Non-alcoholic fatty liver disease; NAFL: nonalcoholic fatty liver; NASH: Nonalcoholic steatohepatitis; DAG: Diacylglycerol; TAG: Triacylglycerol; SFA: Saturated Fatty acids; MUFA: Monounsaturated fatty acids; PC: Phosphatidylcholine; HETE: Hydroxyeicosatetraenoic acid; 5,6-diHETrE : 5,6 dihydroxy- eicosatrienoic acid; 12,13-diHOME: 12,13-dihydroxy-9- octadecenoic acid; CE: Cholesteryl ester; PE: Phosphatidylethanolamine; LA: Linoleic acid (C18:2n-6); DHA: 11,12-diHETrE: 11,12-dihydroxy- eicosatrienoic acid; dhk PGD2: 13,14-dihydro-15-keto prostaglandin D2; 20-COOH AA: 20-carboxy arachidonic acid; SM: Sphingomyelin; PE: Phosphatidylethanolamine; PS: Phosphatidylserine; PI: Phosphatidylinositol.