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

Harshica Fernando, Kamlesh K. Bhopale, Shakuntala Kondraganti, Bhupendra Kaphalia, Ghulam Ansari

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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 3. months 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 3. months 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 3. months. 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.

Original languageEnglish (US)
Pages (from-to)127-137
Number of pages11
JournalToxicology and Applied Pharmacology
Volume255
Issue number2
DOIs
StatePublished - Sep 1 2011

Fingerprint

Liver
Rats
Ethanol
Alcoholic Liver Diseases
Lipids
Plasmas
Magnetic Resonance Spectroscopy
Phosphatidylcholines
Biomarkers
Nuclear magnetic resonance spectroscopy
Inflammation
Maltose
Metabolome
Inbred F344 Rats
Fatty Liver
Principal Component Analysis
Nonesterified Fatty Acids
Oxidative stress
Phosphorus
Protons

Keywords

  • Ethanol
  • Fatty liver
  • Lipidomics
  • Lipids
  • Metabolomics

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Lipidomic changes in rat liver after long-term exposure to ethanol. / Fernando, Harshica; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Kaphalia, Bhupendra; Ansari, Ghulam.

In: Toxicology and Applied Pharmacology, Vol. 255, No. 2, 01.09.2011, p. 127-137.

Research output: Contribution to journalArticle

Fernando, Harshica ; Bhopale, Kamlesh K. ; Kondraganti, Shakuntala ; Kaphalia, Bhupendra ; Ansari, Ghulam. / Lipidomic changes in rat liver after long-term exposure to ethanol. In: Toxicology and Applied Pharmacology. 2011 ; Vol. 255, No. 2. pp. 127-137.
@article{29a3b20c252e4a219b001b110dfc60b1,
title = "Lipidomic changes in rat liver after long-term exposure to ethanol",
abstract = "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 3. months 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 3. months 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 3. months. 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.",
keywords = "Ethanol, Fatty liver, Lipidomics, Lipids, Metabolomics",
author = "Harshica Fernando and Bhopale, {Kamlesh K.} and Shakuntala Kondraganti and Bhupendra Kaphalia and Ghulam Ansari",
year = "2011",
month = "9",
day = "1",
doi = "10.1016/j.taap.2011.05.022",
language = "English (US)",
volume = "255",
pages = "127--137",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Lipidomic changes in rat liver after long-term exposure to ethanol

AU - Fernando, Harshica

AU - Bhopale, Kamlesh K.

AU - Kondraganti, Shakuntala

AU - Kaphalia, Bhupendra

AU - Ansari, Ghulam

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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 3. months 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 3. months 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 3. months. 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.

AB - 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 3. months 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 3. months 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 3. months. 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.

KW - Ethanol

KW - Fatty liver

KW - Lipidomics

KW - Lipids

KW - Metabolomics

UR - http://www.scopus.com/inward/record.url?scp=80051592763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051592763&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2011.05.022

DO - 10.1016/j.taap.2011.05.022

M3 - Article

C2 - 21736892

AN - SCOPUS:80051592763

VL - 255

SP - 127

EP - 137

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 2

ER -