Lipidomics reveal aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis

Wang, Baolong; Zhang, Chang-wen; Wang, Liang; Tang, Kunlong; Tanaka, Naoki; Gonzalez, Frank J.; Xu, Yong; Fang, Zhong‐Ze

doi:10.1080/00498254.2018.1467065

Cited by 14 publications

(13 citation statements)

References 31 publications

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“…Furthermore, a lipidomic study of ANIT-induced intrahepatic cholestasis uncovered the role of the aryl hydrocarbon receptor (AHR) in regulating expression of choline kinase (CHK) in mice. Knockout of the Ahr gene significantly reversed ANIT-induced lipid metabolism via Chka expression, and reversed the intrahepatic cholestasis [96]. Vascular protein sorting-associated protein 33B (VPS33B) is involved in the trafficking of intracellular proteins to distinct organelles.…”

Section: Cholestasismentioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC.

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Section: Cholestasismentioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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“…Lipid species of these plasma samples were measured using Ultraperformance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS) system in Tianjin University. The application studies of this system were shown in previous published papers 19,20 . Firstly, 10 μl of plasma was added to 10 μl of mixed standard solution (containing μg/mL 19:0-19:0 PC, 10 μg/mL 17:0-17:0 PE, 15 μg/mL 12:0 SM, 2μg/mL 19:0 Lyso PC, or 10μg/mL 19:0 ceramide dissolved in isopropanol-acetonitrile solution).…”

Section: Study Protocolmentioning

confidence: 99%

Relationship between Plasma Lipidomics and Carotid Atherosclerotic Plaque

Xie

Myint

Fang

et al. 2020

Preprint

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Abstract Background: The rapidly growing discipline of lipidomics allows the study of a wide spectrum of lipid species in human plasma and provides new insights into the pathogenesis of atherosclerosis. Objective: To explore the roles of plasma lipid components in relation to atherosclerotic plaques.Methods: Ten non-symptomatic persons (age 62.42±3.45) with 2 or more carotid plaques (soft or mixed) and ten apparently healthy controls without any carotid plaque (age 62.82±4.38), were randomly selected as cases and controls from a community-based sample of 1312 persons. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was used to measure lipid components. The difference of lipid species between cases and controls was analyzed by t-test and general linear regression. Results: Among 53 lipid components, significantly elevated plasma levels of one novel individual ceramide species (ceramide 22: 0) were observed in cases compared to the controls (0.59±0.18 versus 0.41±0.10μg/mL, p values<0.05). After adjusting for confounding factors, such as total cholesterol and low-density lipoprotein cholesterol, the results remained significant (p<0.05). 22:0 ceramide was significantly negatively correlated with vegetable intake (r=-0.74, p=0.014).Conclusion: High level of plasma ceramide 22:0 may be a novel risk factor for carotid atherosclerosis in human which independent of cholesterol and low-density lipoprotein cholesterol, it deserves future studies with larger sample size to confirm.

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“…However, the mechanisms underlying ANIT-induced acute cholestasis have remained to be fully elucidated. Due to its similarities with drug-induced cholangiolitic hepatitis in humans, ANIT-induced acute cholestasis has been widely used as a model of acute cholestasis in susceptible species, such as rats (15)(16)(17).…”

Section: Itraq-based Quantitative Proteomics Analysis Of the Hepatoprotective Effect Of Melatonin On Anit-induced Cholestasis In Ratsmentioning

confidence: 99%

iTRAQ‑based quantitative proteomics analysis of the hepatoprotective effect of melatonin on ANIT‑induced cholestasis in rats

Wang

et al. 2021

Exp Ther Med

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The therapeutic effects of melatonin on cholestatic liver injury have received widespread attention recently. The aim of the present study was to investigate the mechanisms of the anti-cholestatic effects of melatonin against α-naphthyl isothiocyanate (ANIT)-induced liver injury in rats and to screen for potential biomarkers of cholestasis through isobaric tags for relative and absolute quantitation (iTRAQ) proteomics. Rats orally received melatonin (100 mg/kg body weight) or an equivalent volume of 0.25% carboxymethyl cellulose sodium salt 12 h after intraperitoneal injection of ANIT (75 mg/kg) and were subsequently sacrificed at 36 h after injection. Liver biochemical indices were determined and liver tissue samples were stained using hematoxylin-eosin staining, followed by iTRAQ quantitative proteomics to identify potential underlying therapeutic mechanisms and biomarkers. The results suggested that the expression levels of alanine transaminase, aspartate aminotransferase, total bilirubin and direct bilirubin were reduced in the rats treated with melatonin. Histopathological observation indicated that melatonin was effective in the treatment of ANIT-induced cholestasis. iTRAQ proteomics results suggested that melatonin-mediated reduction in ANIT-induced cholestasis may be associated with enhanced antioxidant function and relieving abnormal fatty acid metabolism. According to pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes, the major metabolic pathways for the metabolism of melatonin are fatty acid degradation, the peroxisome proliferator-activated receptor signaling pathway, fatty acid metabolism, chemical carcinogenesis, carbon metabolism, pyruvate metabolism, fatty acid biosynthesis and retinol metabolism, as well as drug metabolism via cytochrome P450. Malate dehydrogenase 1 and glutathione S-transferase Yb-3 may serve as potential targets in the treatment of ANIT-induced cholestasis with melatonin.

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Lipidomics reveal aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis

Cited by 14 publications

References 31 publications

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Relationship between Plasma Lipidomics and Carotid Atherosclerotic Plaque

iTRAQ‑based quantitative proteomics analysis of the hepatoprotective effect of melatonin on ANIT‑induced cholestasis in rats

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