TABLE 3.
Application of spatial metabolomics in the study of liver pathophysiology and its implication in zonation
| Sample/study description | Technique | Metabolic differences | Year | References |
|---|---|---|---|---|
| Liver tissue from obese normal, simple steatosis and NASH of class III obese women | MALDI-MSI | • Zonal distributions for 32, 34, and 36 carbon PC in controls lost in simple steatosis or NASH | 2013 | Wattacheril et al131 |
| Primary liver cells from ethanol-treated and silymarin-treated mice | MFD-MD | • Hydrogen peroxide, glutathione, and cysteine were detected simultaneously with high specificity and sensitivity • Identification of significant cell diversity or cell heterogeneity among primary liver cells |
2016 | Li et al132 |
| Liver tissue from mice under HFD, WD, and MCD; human liver biopsies from control, simple steatosis, NASH, and patients with cirrhosis | MALDI-MSI | • Zonal location of arachidonic acid-containing phospholipids; loss of lipid zonation in NASH | 2017 | Hall et al133 |
| Fresh frozen human liver biopsies from obese subjects undergoing bariatric surgery with various degrees of NAFLD | MALDI-TOF MSI | • Marked differences between spatially resolved lipid profiles from nonsteatotic and steatotic tissues • PI and arachidonic acid metabolism in nonsteatotic regions • LDL and VLDL metabolism associated with steatotic tissue |
2018 | Ščupáková et al134 |
| Human liver biopsies from control, simple steatosis, NASH, and patients with cirrhosis | Au-CBS-LDI MS | • Differential distribution of TGs: in low steatosis levels, TG accumulated around the pericentral zone • Macro lipid droplets hepatocytes enriched in fully saturated TG • In NASH and cirrhosis biopsies, TG enrichment observed in ballooned areas |
2019 | Alamri et al135 |
| Liver tissue from mice exposed or not to a single dose of B[a]P | MALDI-MSI | • B[a]P exposed mice with an altered abundance of PI, PC, TG, PE, LysoPEs, LysoPC, FFA, and eicosanoids | 2020 | Li et al136 |
| Liver tissue from mice under HFD | (Au)LDI−MS | • The lipogenic activity is shown to be regiospecific and not always associated with the TG pool size in a given region | 2020 | Downes et al137 |
| OCT-embedded and snap-frozen wild-type mouse and human fibrotic liver tissues | TOF-SIMS | • Different ion species associated as metabolic markers for different liver cell types: – hepatocytes: m/z 255, 279, and 281 – endothelial cells: m/z 60, 76, and 77 – KCs: m/z 134, 181, and 91 • Hepatocytes subclassified by C1–C4 each presenting different metabolic fingerprints: • hepatocytes C1 localized around the CV and near fibrotic boundaries, and associated with metabolic markers m/z 69, 55, and 57 |
2021 | Yuan et a.138 |
| Differentiated human hepatocytes cell line; liver tissue from mice under WD | MALDI-MSI | • Steatotic hepatocytes presented aberrant accumulation of lipid droplets and neutral lipids (TG and DG), and glycerophospholipid ER-enrichment • Inflammatory steatotic hepatocytes with increased sphingomyelins |
2021 | Rappez et al139 |
| Liver tissues from mice exposed to third-hand smoke treated or not with antioxidants | LDI-MSI | • Third-hand smoke-exposed mice presented increased TG and decreased PC and SM lipid species, accumulating in larger and more abundant lipid droplets • Third-hand smoke mainly dysregulated glutathione metabolism, D-glutamine and D-glutamate metabolism, and oxidative phosphorylation |
2021 | Torres et al140 |
| Liver tissue from mice under HFD treated with Eurycoma longifolia | DESI-MSI | • E. longifolia downregulated lipid accumulation and FA biosynthesis, and induced changes in amino acids, organic acids, phospholipids, and glycerolipids | 2021 | Zhang et al141 |
| Liver tissue from mice exposed to aristolochic acid I | Atmospheric pressure-MALDI-MSI | • Aristolochic acid I-induced hepatotoxicity associated with changes in taurine, hypotaurine, glycerophospholipid, D-glutamine, D-glutamate, and arachidonic acid metabolisms | 2021 | Guo et al142 |
| Liver tissues from mice under LFD, HFD, and WD; human FFPE liver biopsy samples from NASH patients | MALDI-MSI | • N-glycan structures upregulated in portal triad area • N-glycosylation modifications correlated with fibrosis score and liver histology changes |
2022 | Ochoa-rios et al143 |
| Liver tissue from mice under fasting conditions, ND, and HFD | MALDI-MSI | • Hepatocyte FA enrichment dependent on proximity to vasculature • HFD disrupted tissue metabolic compartmentalization • Lipid droplets accumulated away from the vasculature and glutathione increased in extravascular regions • HFD associated with oxidative stress, PPP, and purine metabolism |
2022 | Stopka et al70 |
Abbreviations: (Au)LDI-MS, gold-laser desorption/ionization mass spectrometry; Au-CBS-LDI MS, sodium-doped gold-assisted laser desorption ionization mass spectrometry; B[a]P, benzo[a]pyrene; CV, central vein; DG, diglyceride; ER, endoplasmic reticulum; FA, fatty acid; FFA, free fatty acid; FFPE, formalin-fixed paraffin-embedded; HFCD, high-fat choline-deficient diet; HFD, high-fat diet; HFHD, high-fat high-calorie diet; LFD, low-fat diet; MALDI, matrix-assisted laser desorption/ionization; MCD, methionine–choline-deficient diet; MFD-MD, multicolor fluorescence detection-based microfluidic device; MSI, mass spectrometry imaging; OCT, optimal cutting temperature compound; PC, phosphatidylcholine; PE, phosphotidylethanolamine; PI, phosphatidylinositol; PPP, pentose phosphate pathway; SIMS, secondary ion mass spectrometry; TG, triglyceride; TOF, time-of-flight; WD, Western diet.