Lipidomic changes in rat liver after long-term exposure to ethanol

• Published in: Toxicology and applied pharmacology Vol. 255; no. 2; pp. 127 - 137
• Main Authors: Fernando, Harshica, Bhopale, Kamlesh K., Kondraganti, Shakuntala, Kaphalia, Bhupendra S., Shakeel Ansari, G.A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.09.2011; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Alanine Transaminase - blood; Alcoholism and acute alcohol poisoning; ALCOHOLS; ANIMALS; Aspartate Aminotransferases - blood; Biological and medical sciences; BIOLOGICAL MARKERS; BODY; Body Weight - drug effects; CARBOHYDRATES; CARBOXYLIC ACIDS; CHEMICAL REACTIONS; DIGESTIVE SYSTEM; DISACCHARIDES; DISEASE INCIDENCE; DISEASES; ELEMENTS; ESTERS; ETHANOL; Ethanol - administration & dosage; Ethanol - toxicity; Fatty liver; Gastroenterology. Liver. Pancreas. Abdomen; GLANDS; HYDROXY COMPOUNDS; Immunohistochemistry; INFLAMMATION; LECITHINS; Lipid Metabolism - drug effects; Lipidomics; LIPIDS; LIVER; Liver - drug effects; Liver - metabolism; Liver Diseases, Alcoholic - enzymology; Liver Diseases, Alcoholic - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; MAGNETIC RESONANCE; Magnetic Resonance Spectroscopy; Male; MALTOSE; MAMMALS; Medical sciences; Metabolomics; Metabolomics - methods; MORTALITY; NONMETALS; NUCLEAR MAGNETIC RESONANCE; OLIGOSACCHARIDES; Organ Size - drug effects; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC PHOSPHORUS COMPOUNDS; ORGANS; Other diseases. Semiology; OXIDATION; Oxidative Stress - drug effects; PATHOLOGICAL CHANGES; PHOSPHOLIPIDS; PHOSPHORUS; PLASMA; Principal Component Analysis; RATS; Rats, Inbred F344; RESONANCE; RODENTS; SACCHARIDES; SPECTROSCOPY; SYMPTOMS; TIME DEPENDENCE; Toxicology; TRIGLYCERIDES; VERTEBRATES; Metabolomics; Lipidomics; Lipids; Fatty liver; Ethanol; Rat; Digestive system; Liver; Rodentia; Hepatic disease; Exposure; Long term; Alcoholic beverage; Vertebrata; Mammalia; Animal; Metabonomics; Digestive diseases
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2011.05.022

Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose–dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD. ► Long term exposure to ethanol was studied. ► A nuclear magnetic resonance (NMR) spectroscopy based lipidomic approach was used. ► We examined the clustering pattern of the NMR data with principal component analysis. ► NMR data were compared with histology and immunohistochemistry data. ► Biochemical parameters were compared with the observed NMR lipid data.