Introduction
Metabolic changes of lipids in non-alcoholic fatty liver disease
Lipolysis of adipose tissue
Lipid uptake
De novo lipogenesis (DNL) and triglyceride synthesis
Fatty acid oxidation (FAO)
Very low-density lipoprotein (VLDL) excretion
Mechanisms of lipotoxicity
Various lipid species are involved in non-alcoholic fatty liver disease
References | Year | Study cohort | Technique | Main findings |
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[43] | 2007 | Normal (n = 9) NAFL (n = 9) NASH (n = 9) | TLC | 1. Increased TG and DG, but unaltered FFAs in both NAFL and NASH cohorts compared with control 2. FC and TG/DG ratio progressively increased from normal liver to NAFL to NASH. However, the total CE content was not significantly changed in either NAFL or NASH 3. n-6 and n-3 PUFAs within hepatic FFAs exhibited trends of stepwise decrease from control to NAFL to NASH 4. PUFAs in DG and TG decreased significantly, meanwhile, SFAs and MUFAs in DG and TG showed trends for increase in NAFL and NASH 5. The total PC decreased in both NAFL and NASH, but no significant changes in PS or CL 6. AA was relatively depleted from most lipid species |
[44] | 2015 | Normal (n = 31) Steatosis (n = 17) NASH (n = 20) Cirrhosis (n = 20) | LC–MS | 1. TG was higher in NASH and steatosis cohorts compared with normal 2. TG contained higher amounts of short-chain FA- and SFA, lower amounts of PUFA in NASH compared with steatosis 3. PUFA-containing LyPEs were significantly increased in steatosis, but not in NASH 4. Almost all lipids except for eicosanoids and certain GPLs (e.g. PIs, ether-linked PEs) were lower in the cirrhotic than in normal samples 5. NASH demonstrated higher amounts of many sphingolipids and the greatest distinction between NASH and steatosis was in very-long-chain dihydroceramides and 1-deoxydihydroceramides |
[45] | 2017 | Control (n = 7) NAFL (n = 39) NASH (n = 15) | GC/LC–MS | 1. The increased FAs in NASH (14:0, 16:0, 16:1 n-7, 18:1 n-7, 18:1 n-9 and 18:2 n-6) belong to the long-chain FA synthesis pathway and related to the decreased ELOVL6 activity and increased FADS2 and SCD1 activities 2. The significantly decreased eicosanoid precursors (AA, EPA and DHA) is related to the decrease in FADS1 activity in NASH compared with control 3. The deficiency in the synthesis of polyunsaturated long-chain FA causes a decrease in phospholipids in NASH patients |
[46] Focused on mitochondrial lipids | 2018 | Control (n = 16) NAFL (n = 10) NASH (n = 32) | LC–MS | 1. The levels of TG, DG, dihydroceramide, cholesterol, CE, acylcarnitine, dihexosylceramide, CL and ubiquinone were significantly higher in NAFL and/or NASH compared with control 2. SFAs (e.g., 14:0, 17:0, and 18:0) in TG increased significantly in NASH compared with control 3. Only acylcarnitine and dihexosylceramide demonstrated a significant increase in NASH compared with NAFL 4. Hepatic CL and ubiquinone accumulated in NAFL and NASH, and levels of acylcarnitine increased in NASH, indicating the mitochondrial dysfunction. However, the percentage of 18:2 FA in CL, the most abundant FA composition in CL, was lower in NASH 5. Among the most abundant FAs in CEs, 16:1 and 18:2 FAs were increased, while 16:0 and 18:1 FAs were decreased in NASH compared with control. Meanwhile, 16:0 FA in CEs was also significantly lower in NAFL compared with control 6. The percentage of polyunsaturated AA in TG showed a stepwise decrease from Control to NAFL to NASH 7. Only dihydroceramide and dihexosylceramide were significantly different (increased) in the sphingolipids class between the control and NAFL/NASH 8. NAFL and NASH demonstrated higher amounts of MUFAs (16:1 and 18:1), however lower amounts of SFA (18:0), diunsaturated (DUFA, 18:2), and long-chain PUFAs (20:4, 22:5, and 22:6) in DGs 9. Several phospholipid species comprising DHA decreased during the progression of NAFLD, including PC(P-16:0/22:6), LyPC (22:6), and PE(18:1, 22:6) |
References | Year | Study cohort | Technique | Main findings |
---|---|---|---|---|
[47] | 2009 | Normal (n = 50) NAFL (n = 25) NASH (n = 50) | TLC | 1. The total plasma MUFAs, which were driven by palmitoleic (16:1) and oleic (18:1) acids, were significantly increased in NAFL and NASH 2. The total SFAs were higher in both NAFL and NASH compared with control 3. The levels of DG and TG were significantly lower in NAFL and NASH compared with control 4. The total n-3 and n-6 PUFAs content progressively decreased in most lipid classes (including FFAs, TG, PC, LyPC) 5. Linoleic acid (8:2) was decreased with a concomitant increase in γ-linolenic (18:3) and dihomo γ-linolenic (20:3) acids in both NAFL and NASH 6. The plasma levels of AA (prostaglandin [PG]-M, PGB2, PGD2, PGE2, PGF2, and thromboxane A2) were not significantly different among normal, NAFL and NASH 7. The plasma levels of several products of the LOX pathway (5-HETE, 8-HETE, and 15-HETE) were significantly higher in NASH compared with NAFL/normal |
[44] | 2015 | Normal (n = 31) Steatosis (n = 17) NASH (n = 20) Cirrhosis (n = 20) | LC–MS | 1. The plasma levels of several eicosanoids and FFAs were increased, whereas the plasma levels of many plasma neutral lipids, GPLs, and some sterols were reduced in cirrhosis, but not in NASH 2. Cirrhotic patients demonstrated decreased plasma levels of most SMs, long-chain bases, and glycolytic/TCA cycle metabolites, while increased plasma levels of several glucosylceramide species and nucleotides 3. NASH patients exhibited elevated ceramides, dihydroceramides, and 1-deoxy-dihydroceramides and 1-deoxy-ceramides 4. CEs, some sphingolipids and GPLs (e.g. PUFA PEs and those containing ether-linked moieties were increased), and the aqueous metabolite F16BP could distinguish NASH from steatosis 5. Sphingolipids and GPLs, which provide the best clustering by linear discriminant analysis, could distinguish all the histological states |
[48] | 2016 | Non-NAFLD (n = 132) NAFL (n = 117) NASH (n = 69) | UPLC-MS | 1. NASH was significantly associated with the elevated concentrations of saturated and monounsaturated TGs in the serum 2. NASH exhibited significantly reduced levels of SMs and lyPC compared with other groups 3. The absolute concentrations of saturated and monounsaturated TGs were significantly increased in NASH compared with other groups 4. The levels of saturated and monounsaturated TGs were elevated in NASH compared with non-NAFLD, and was inversely correlated with the number of double bonds |
[49] Focused on circulating phospholipids | 2018 | Normal (n = 28) NAFL (n = 25) NASH (n = 42) | LC–MS | 1. Increased circulating PC and SM, while decreased PE in NAFL and NASH 2. NASH patients demonstrated elevated PE compared with NAFL subjects 3. LyPE was significantly decreased in NAFL and NASH compared with control 4. The levels of PI and plasmalogens were not significantly different among all groups 5. NAFLD patients with hypertension demonstrated higher amounts of circulating PC and SM than NAFLD patients without hypertension 6. Diabetic (n = 18) and non-diabetic NAFLD patients (n = 49) showed no difference in the total phospholipids, including PC, PE and SM |
[46] Focused on mitochondr-ial lipids | 2018 | Control (n = 16) NAFL (n = 10) NASH (n = 32) | LC–MS | Acylcarnitines were increased in NASH compared with control |