Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study[S]

Chronic alcohol consumption is associated with fatty liver disease in mammals. The object of this study was to gain an understanding of dysregulated lipid metabolism in alcohol-fed C57BL/6 mice using a targeted lipidomic approach. Liquid chromatography tandem mass spectrometry was used to analyze several lipid classes, including free fatty acids, fatty acyl-CoAs, fatty acid ethyl esters, sphingolipids, ceramides, and endocannabinoids, in plasma and liver samples from control and alcohol-fed mice. The interpretation of lipidomic data was augmented by gene expression analyses for important metabolic enzymes in the lipid pathways studied. Alcohol feeding was associated with i) increased hepatic free fatty acid levels and decreased fatty acyl-CoA levels associated with decreased mitochondrial fatty acid oxidation and decreased fatty acyl-CoA synthesis, respectively; ii) increased hepatic ceramide levels associated with higher levels of the precursor molecules sphingosine and sphinganine; and iii) increased hepatic levels of the endocannabinoid anandamide associated with decreased expression of its catabolic enzyme fatty acid amide hydrolase. The unique combination of lipidomic and gene expression analyses allows for a better mechanistic understanding of dysregulated lipid metabolism in the development of alcoholic fatty liver disease.

• Publication year

  2011

• Venue

  Journal of Lipid Research

• Publication date

  2011-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1194/jlr.M017368PMID 21856784PMCID PMC3196234
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Epidemiology of Alcoholic Liver Disease

  2018cited by this paper
• Endocannabinoids in liver disease

  2011cited by this paper
• Ethanol-induced alterations in fatty acid-related lipids in serum and tissues in mice.

  2011cited by this paper
• Metabonomic investigation of liver profiles of nonpolar metabolites obtained from alcohol-dosed rats and mice using high mass accuracy MSn analysis.

  2011cited by this paper
• The Role of Lipid Metabolism in the Pathogenesis of Alcoholic and Nonalcoholic Hepatic Steatosis

  2010cited by this paper
• Sphingolipids and insulin resistance: the five Ws

  2010cited by this paper
• Endocannabinoids and Their Role in Fatty Liver Disease

  2010cited by this paper
• FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase.

  2010cited by this paper
• Pathogenesis of alcoholic liver disease: the role of nuclear receptors

  2010cited by this paper
• Liver fatty acid-binding protein and obesity.

  2010cited by this paper
• Ethanol elevates physiological all‐trans‐retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity

  2010cited by this paper
• High fat diet induces ceramide and sphingomyelin formation in rat’s liver nuclei

  2010cited by this paper
• ¹H and ³¹P NMR lipidome of ethanol-induced fatty liver.

  2010cited by this paper
• Insulin- and leptin-regulated fatty acid uptake plays a key causal role in hepatic steatosis in mice with intact leptin signaling but not in ob/ob or db/db mice.

  2010cited by this paper
• Inhibitory effect of ethanol on AMPK phosphorylation is mediated in part through elevated ceramide levels.

  2010cited by this paper
• Hepatic long-chain acyl-CoA synthetase 5 mediates fatty acid channeling between anabolic and catabolic pathways[S]

  2010cited by this paper
• Bioactive sphingolipids: metabolism and function This work was supported by National Institutes of Health Grants GM-43825 and CA-87584. Published, JLR Papers in Press, November 17, 2008.

  2009cited by this paper
• “Hypothesis of Seven Balances”: Molecular Mechanisms behind Alcoholic Liver Diseases and Association with PPARα

  2009cited by this paper
• Relationship between Dietary Beef, Fat, and Pork and Alcoholic Cirrhosis

  2009cited by this paper
• Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal

  2009cited by this paper
• Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention.

  2009cited by this paper
• Adenosine signaling contributes to ethanol-induced fatty liver in mice.

  2009cited by this paper
• Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome.

  2009cited by this paper
• Metabolomics, a novel tool for studies of nutrition, metabolism and lipid dysfunction.

  2009cited by this paper
• Liver-specific Loss of Long Chain Acyl-CoA Synthetase-1 Decreases Triacylglycerol Synthesis and β-Oxidation and Alters Phospholipid Fatty Acid Composition*

  2009cited by this paper
• Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver.

  2008cited by this paper
• Endocannabinoids: synthesis and degradation.

  2008cited by this paper
• Ethanol-induced cytotoxicity in rat pancreatic acinar AR42J cells: role of fatty acid ethyl esters.

  2007cited by this paper
• Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice.

  2007cited by this paper
• Rat Long Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Uptake and Partitioning to Cellular Triacylglycerol in McArdle-RH7777 Cells*

  2006cited by this paper
• Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy.

  2006cited by this paper
• Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: role of nonoxidative metabolism.

  2006cited by this paper
• Retinoid Absorption and Storage Is Impaired in Mice Lacking Lecithin:Retinol Acyltransferase (LRAT)*

  2005cited by this paper
• Fatty acid ethyl esters: markers of alcohol abuse and alcoholism.

  2004cited by this paper
• Liver fatty acid‐binding protein is required for high rates of hepatic fatty acid oxidation but not for the action of PPAR‐α in fasting mice

  2004cited by this paper
• The influence of undernutrition during gestation on skeletal muscle cellularity and on the expression of genes that control muscle growth

  2004cited by this paper
• Role of different dietary fatty acids in the pathogenesis of experimental alcoholic liver disease.

  2004cited by this paper
• Some novel insights into the pathogenesis of alcoholic steatosis.

  2004cited by this paper
• Liver Peroxisome Proliferator-activated Receptor γ Contributes to Hepatic Steatosis, Triglyceride Clearance, and Regulation of Body Fat Mass*

  2003cited by this paper
• The mechanisms of action of PPARs.

  2002cited by this paper
• Fatty acid ethyl esters: recent observations.

  2002cited by this paper
• Characterization of enzymes involved in formation of ethyl esters of long-chain fatty acids in humans.

  2001cited by this paper
• Purification and characterization of rat hepatic microsomal low molecular weight fatty acid ethyl ester synthase and its relationship to carboxylesterases

  2001cited by this paper
• A new mathematical model for relative quantification in real-time RT-PCR.

  2001cited by this paper
• Activation of neutral sphingomyelinase participates in ethanol-induced apoptosis in Hep G2 cells.

  2000cited by this paper
• No Significant Difference

  1999cited by this paper
• Long-term alcohol consumption increases matrix metalloproteinase-2 activity in rat aorta.

  1999cited by this paper
• The Fatty Acid Transport Protein (FATP1) Is a Very Long Chain Acyl-CoA Synthetase*

  1999cited by this paper
• Fatty acid ethyl esters: potentially toxic products of myocardial ethanol metabolism.

  1998cited by this paper
• Ethyl palmitate and ethyl oleate are the predominant fatty acid ethyl esters in the blood after ethanol ingestion and their synthesis is differentially influenced by the extracellular concentrations of their corresponding fatty acids.

  1997cited by this paper
• Effects of dietary polyunsaturated fat on ethanol-induced Ito cell activation.

  1996cited by this paper
• Peroxisome proliferators induce mouse liver stearoyl-CoA desaturase 1 gene expression.

  1996cited by this paper
• Identification of a Peroxisome Proliferator-responsive Element Upstream of the Human Peroxisomal Fatty Acyl Coenzyme A Oxidase Gene (*)

  1996cited by this paper
• Transcriptional control of the stearoyl-CoA desaturase-1 gene by polyunsaturated fatty acids.

  1994cited by this paper
• Epidemiology of alcoholic liver disease.

  1993cited by this paper
• Preferential alcoholic embryopathy: effects of liquid diets.

  1992cited by this paper
• Epidemiology of Alcoholic Liver Disease

  1988cited by this paper
• Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators.

  1986cited by this paper
• Hepatic vitamin A depletion in alcoholic liver injury.

  1982cited by this paper
• Mechanism of rat liver microsomal stearyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid.

  1976cited by this paper
• Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate new liquid diet.

  1967cited by this paper
• A simple method for the isolation and purification of total lipides from animal tissues.

  1957cited by this paper

• Sphingolipids in Emotional Well‐Being

  2026cites this paper
• Hepatic response to ethanol feeding in a hepatocyte-specific fatty acid binding protein-4 knock out mouse model.

  2025cites this paper
• Protective effects of hot water extract from glasswort (Salicornia herbacea L.) on ethanol-induced hepatic injury in mice

  2025cites this paper
• MicroRNA-Mediated Metabolic Control in HCC: From Molecular Networks to Therapy.

  2025cites this paper
• Sex-Specific Effect of Ethanol on Colon Content Lipidome in a Mice Model Using Nontargeted LC/MS

  2024cites this paper
• SPHINGOLIPIDS ARE DEPLETED IN ALCOHOL-RELATED LIVER FIBROSIS.

  2023cites this paper
• Lipidomic Analysis of Liver Lipid Droplets after Chronic Alcohol Consumption with and without Betaine Supplementation

  2023influential citation
• Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses

  2023cites this paper
• Immunometabolic capacities of nutritional fatty acids in regulation of inflammatory bone cell interaction and systemic impact of periodontal infection

  2023cites this paper
• Oxidative Stress and Redox Signaling in the Pathophysiology of Liver Diseases.

  2022cites this paper
• Pathogenesis of Alcohol-Associated Fatty Liver: Lessons From Transgenic Mice

  2022cites this paper
• Metabolomic Analysis Uncovers Lipid and Amino Acid Metabolism Disturbance During the Development of Ascites in Alcoholic Liver Disease

  2022cites this paper
• Circadian clock disruption aggravates alcohol liver disease in an acute mouse model

  2022cites this paper
• Hepatoprotective effects of sea cucumber ether-phospholipids against alcohol-induced lipid metabolic dysregulation and oxidative stress in mice.

  2022cites this paper
• Alcohol induced hepatic retinoid depletion is associated with the induction of multiple retinoid catabolizing cytochrome P450 enzymes

  2022cites this paper
• Lipidomics for the Prediction of Progressive Liver Disease in Patients with Alcohol Use Disorder

  2022cites this paper
• Lipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage

  2021cites this paper
• Association of the Liver and Plasma Lipidomes with the Histological Stage of Alcohol-Related Liver Disease

  2021cites this paper
• ZFP36L1 regulates Fgf21 mRNA turnover and modulates alcoholic hepatic steatosis and inflammation in mice

  2021cites this paper
• FOXO4 ameliorates alcohol-induced chronic liver injury via inhibiting NF-κB and modulating gut microbiota in C57BL/6J mice.

  2021cites this paper
• Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder.

  2021cites this paper
• Stress‐Responsive Gene FK506‐Binding Protein 51 Mediates Alcohol‐Induced Liver Injury Through the Hippo Pathway and Chemokine (C‐X‐C Motif) Ligand 1 Signaling

  2021cites this paper
• Comprehensive lipidomics reveals reduced hepatic lipid turnover in NAFLD during alcohol intoxication

  2021influential citation
• Comprehensive lipidomics reveals phenotypic differences in hepatic lipid turnover in ALD and NAFLD during alcohol intoxication

  2021cites this paper
• Convergent somatic mutations in metabolism genes in chronic liver disease

  2021cites this paper
• Retinol-binding protein 2 (RBP2) binds monoacylglycerols and modulates gut endocrine signaling and body weight

  2020cites this paper
• Alcohol effects on hepatic lipid metabolism

  2020cites this paper
• Serotonin – lipid interactions and their role in behavior

  2020cites this paper
• Effect of probiotics Lactobacillus paracasei GKS6, L. plantarum GKM3, and L. rhamnosus GKLC1 on alleviating alcohol-induced alcoholic liver disease in a mouse model

  2020cites this paper
• Dietary citrus peel essential oil ameliorates hypercholesterolemia and hepatic steatosis by modulating lipid and cholesterol homeostasis.

  2020cites this paper
• Alcohol and Liver Clock Disruption Increase Small Droplet Macrosteatosis, Alter Lipid Metabolism and Clock Gene mRNA Rhythms, and Remodel the Triglyceride Lipidome in Mouse Liver

  2020cites this paper
• Metabolic alterations and vulnerabilities in hepatocellular carcinoma

  2020cites this paper
• Lipidomic Profiling Reveals Disruption of Lipid Metabolism in Valproic Acid-Induced Hepatotoxicity

  2019cites this paper
• Constitutive androstane receptor mediates pcb-induced disruption of retinoid homeostasis.

  2019cites this paper
• Hepatic stellate cell activation: A source for bioactive lipids.

  2019cites this paper
• Enhanced Alcohol Preference and Anxiolytic Alcohol Effects in Niemann-Pick Disease Model in Mice

  2019influential citation
• Dietary Macronutrient Composition Determines the Contribution of DGAT1 to Alcoholic Steatosis

  2018influential citation
• The role of sphingolipids in psychoactive drug use and addiction

  2018cites this paper
• β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway.

  2018cites this paper
• Inhibition of Hepatotoxicity by a LXR Inverse Agonist in a Model of Alcoholic Liver Disease.

  2018cites this paper
• The Hepatic Lipidome: A Gateway to Understanding the Pathogenes is of Alcohol-Induced Fatty Liver.

  2017cites this paper
• Structure, Function and Metabolism of Hepatic and Adipose Tissue Lipid Droplets: Implications in Alcoholic Liver Disease.

  2017cites this paper
• Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling

  2017cites this paper
• Editorial: New Insights into Mechanisms of Alcohol-Induced Fatty Liver.

  2017cites this paper
• Increased de novo ceramide synthesis and accumulation in failing myocardium.

  2017cites this paper
• The effect of alcohol on the differential expression of cluster of differentiation 14 gene, associated pathways, and genetic network

  2017cites this paper
• Mitochondria-targeted ubiquinone (MitoQ) enhances acetaldehyde clearance by reversing alcohol-induced posttranslational modification of aldehyde dehydrogenase 2: A molecular mechanism of protection against alcoholic liver disease

  2017cites this paper
• Increased de novo ceramide synthesis and accumulation in failing myocardium.

  2017cites this paper
• Alcohol, Adipose Tissue and Lipid Dysregulation

  2017cites this paper
• Oral Administration of β-Glucosylceramide for the Treatment of Insulin Resistance and Nonalcoholic Steatohepatitis: Results of a Double-Blind, Placebo-Controlled Trial

  2017influential citation
• Cyp8b1 ablation prevents Western diet-induced weight gain and hepatic steatosis because of impaired fat absorption.

  2017cites this paper
• Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

  2016cites this paper
• The Role of Ceramide in the Pathogenesis of Alcoholic Liver Disease.

  2016cites this paper
• Susceptibility of Different Mouse Wild Type Strains to Develop Diet-Induced NAFLD/AFLD-Associated Liver Disease

  2016influential citation
• Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance.

  2016cites this paper
• The Role of CD36 in the Pathogenesis of Alcohol-Related Disease

  2016cites this paper
• Adipocyte‐specific overexpression of retinol‐binding protein 4 causes hepatic steatosis in mice

  2016influential citation
• High resolution metabolomics technology reveals widespread pathway changes of alcoholic liver disease.

  2016cites this paper
• Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4α and Protects Against Alcohol- and MCD diet-induced Liver Injury

  2016cites this paper
• Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation

  2016cites this paper
• Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment

  2015cites this paper
• The Role of Dependence in Alcohol Reinforcement: Neurobehavioral Mechanisms

  2015cites this paper
• Chronic alcohol consumption enhances iNKT cell maturation and activation.

  2015cites this paper
• Fatty Acid Ethyl Esters Disrupt Neonatal Alveolar Macrophage Mitochondria and Derange Cellular Functioning

  2015influential citation
• Supplementation of L-Alanyl-L-Glutamine and Fish Oil Improves Body Composition and Quality of Life in Patients With Chronic Heart Failure

  2015cites this paper
• Actions of β-apo-carotenoids in differentiating cells: differential effects in P19 cells and 3T3-L1 adipocytes.

  2015cites this paper
• Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation

  2015cites this paper
• Increased hepatocellular protein carbonylation in human end-stage alcoholic cirrhosis.

  2015cites this paper
• Alterations of plasma glycerophospholipid and sphingolipid species in male alcohol-dependent patients.

  2015cites this paper
• Insulin resistance in clinical and experimental alcoholic liver disease

  2015cites this paper
• CYP2E1- and TNFalpha/LPS-Induced Oxidative Stress and MAPK Signaling Pathways in Alcoholic Liver Disease

  2015cites this paper
• Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss

  2015cites this paper
• Absence of Perilipin 2 Prevents Hepatic Steatosis, Glucose Intolerance and Ceramide Accumulation in Alcohol-Fed Mice

  2014cites this paper
• Cardiac dysfunction in β-carotene-15,15'-dioxygenase-deficient mice is associated with altered retinoid and lipid metabolism.

  2014cites this paper
• Loss of β-carotene 15,15'-oxygenase in developing mouse tissues alters esterification of retinol, cholesterol and diacylglycerols.

  2014cites this paper
• Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation.

  2014cites this paper
• Regulation of glucose and lipid homeostasis by adiponectin: effects on hepatocytes, pancreatic β cells and adipocytes.

  2014cites this paper
• CD36-deficient mice are resistant to alcohol- and high-carbohydrate-induced hepatic steatosis[S]

  2014cites this paper
• Lipoprotein lipase activity is required for cardiac lipid droplet production[S]

  2014cites this paper
• Retinoid acid-related orphan receptor γ, RORγ, participates in diurnal transcriptional regulation of lipid metabolic genes

  2014cites this paper
• Preservation of hepatocyte nuclear factor-4α contributes to the beneficial effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid dyshomeostasis in rats.

  2013cites this paper
• Chronic ethanol consumption increases cardiomyocyte fatty acid uptake and decreases ventricular contractile function in C57BL/6J mice.

  2013influential citation
• Hepatic retinoid stores are required for normal liver regeneration[S]

  2013cites this paper
• Lipidomics in nutrition and food research.

  2013influential citation
• Chronic ethanol consumption alters mammalian gastrointestinal content metabolites.

  2013cites this paper
• Susceptibility of L-FABP−/− mice to oxidative stress in early-stage alcoholic liver[S]

  2013cites this paper
• Synthesis of fatty acid ethyl esters in mammalian tissues after ethanol exposure: a systematic review of the literature

  2013cites this paper
• Transgenic biosynthesis of polyunsaturated fatty acids: a sustainable biochemical engineering approach for making essential fatty acids in plants and animals.

  2013cites this paper
• Increased dietary fat contributes to dysregulation of the LKB1/AMPK pathway and increased damage in a mouse model of early-stage ethanol-mediated steatosis.

  2013cites this paper
• Adipose-specific Lipoprotein Lipase Deficiency More Profoundly Affects Brown than White Fat Biology*

  2013cites this paper
• Altered hepatic retinyl ester concentration and acyl composition in response to alcohol consumption.

  2013cites this paper
• Altered hepatic retinyl ester concentration and acyl composition in response to alcohol consumption.

  2013cites this paper
• Chronic Alcohol Consumption Impairs Distribution and Compromises Circulation of B Cells in B16BL6 Melanoma-Bearing Mice

  2012cites this paper
• Understanding Typhoid : A Mouse Model of Salmonella typhi Infection

  2012cites this paper
• Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice.

  2012cites this paper
• Targeted Chiral Analysis of Bioactive Arachidonic Acid Metabolites Using Liquid-Chromatography-Mass Spectrometry

  2012cites this paper
• Diacylglycerol acyl transferase 1 overexpression detoxifies cardiac lipids in PPARγ transgenic mice[S]

  2012cites this paper
• Characterization of 4-HNE Modified L-FABP Reveals Alterations in Structural and Functional Dynamics

  2012cites this paper
• Lipidomic profiling reveals protective function of fatty acid oxidation in cocaine-induced hepatotoxicity[S]

  2012cites this paper
• current as B Cells in B 16 BL 6 Melanoma-Bearing Mice ofDistribution and Compromises Circulation Chronic Alcohol Consumption Impairs

  2012cites this paper