1H and 31P NMR lipidome of ethanol-induced fatty liver

Harshica Fernando, Shakuntala Kondraganti, Kamlesh K. Bhopale, David E. Volk, Muniasamy Neerathilingam, Bhupendra Kaphalia, Bruce A. Luxon, Paul J. Boor, Ghulam Ansari

Research output: Contribution to journalArticle

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Abstract

Background: Hepatic steatosis (fatty liver), an early and reversible stage of alcoholic liver disease, is characterized by triglyceride deposition in hepatocytes, which can advance to steatohepatitis, fibrosis, cirrhosis, and ultimately to hepatocellular carcinoma. In the present work, we studied altered plasma and hepatic lipid metabolome (lipidome) to understand the mechanisms and lipid pattern of early-stage alcohol-induced-fatty liver.Methods: Male Fischer 344 rats were fed 5% alcohol in a Lieber-DeCarli diet. Control rats were pair-fed an equivalent amount of maltose-dextrin. After 1 month, animals were killed and plasma collected. Livers were excised for morphological, immunohistochemical, and biochemical studies. The lipids from plasma and livers were extracted with methyl-tert-butyl ether and analyzed by 750/800 MHz proton nuclear magnetic resonance (1H NMR) and phosphorus (31P) NMR spectroscopy on a 600 MHz spectrometer. The NMR data were then subjected to multivariate statistical analysis.Results: Hematoxylin and Eosin and Oil Red O stained liver sections showed significant fatty infiltration. Immunohistochemical analysis of liver sections from ethanol-fed rats showed no inflammation (absence of CD3 positive cells) or oxidative stress (absence of malondialdehyde reactivity or 4-hydroxynonenal positive staining). Cluster analysis and principal component analysis of 1H NMR data of lipid extracts of both plasma and livers showed a significant difference in the lipid metabolome of ethanol-fed versus control rats. 31P NMR data of liver lipid extracts showed significant changes in phospholipids similar to 1H NMR data. 1H NMR data of plasma and liver reflected several changes, while comparison of 1H NMR and 31P NMR data offered a correlation among the phospholipids.Conclusions: Our results show that alcohol consumption alters metabolism of cholesterol, triglycerides, and phospholipids that could contribute to the development of fatty liver. These studies also indicate that fatty liver precedes oxidative stress and inflammation. The similarities observed in plasma and liver lipid profiles offer a potential methodology for detecting early-stage alcohol-induced fatty liver disease by analyzing the plasma lipid profile.

Original languageEnglish (US)
Pages (from-to)1937-1947
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume34
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Metabolome
Fatty Liver
Liver
Ethanol
Nuclear magnetic resonance
Lipids
Plasmas
Phospholipids
Alcohols
Rat control
Triglycerides
Oxidative Stress
Fibrosis
Magnetic Resonance Spectroscopy
Oxidative stress
Inflammation
Proton Magnetic Resonance Spectroscopy
Liver Extracts
Alcoholic Liver Diseases
Maltose

Keywords

  • Ethanol
  • Fatty liver
  • Lipidomics
  • Lipids
  • Metabolomics

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology
  • Medicine(all)

Cite this

1H and 31P NMR lipidome of ethanol-induced fatty liver. / Fernando, Harshica; Kondraganti, Shakuntala; Bhopale, Kamlesh K.; Volk, David E.; Neerathilingam, Muniasamy; Kaphalia, Bhupendra; Luxon, Bruce A.; Boor, Paul J.; Ansari, Ghulam.

In: Alcoholism: Clinical and Experimental Research, Vol. 34, No. 11, 11.2010, p. 1937-1947.

Research output: Contribution to journalArticle

Fernando, H, Kondraganti, S, Bhopale, KK, Volk, DE, Neerathilingam, M, Kaphalia, B, Luxon, BA, Boor, PJ & Ansari, G 2010, '1H and 31P NMR lipidome of ethanol-induced fatty liver', Alcoholism: Clinical and Experimental Research, vol. 34, no. 11, pp. 1937-1947. https://doi.org/10.1111/j.1530-0277.2010.01283.x
Fernando, Harshica ; Kondraganti, Shakuntala ; Bhopale, Kamlesh K. ; Volk, David E. ; Neerathilingam, Muniasamy ; Kaphalia, Bhupendra ; Luxon, Bruce A. ; Boor, Paul J. ; Ansari, Ghulam. / 1H and 31P NMR lipidome of ethanol-induced fatty liver. In: Alcoholism: Clinical and Experimental Research. 2010 ; Vol. 34, No. 11. pp. 1937-1947.
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AU - Bhopale, Kamlesh K.

AU - Volk, David E.

AU - Neerathilingam, Muniasamy

AU - Kaphalia, Bhupendra

AU - Luxon, Bruce A.

AU - Boor, Paul J.

AU - Ansari, Ghulam

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N2 - Background: Hepatic steatosis (fatty liver), an early and reversible stage of alcoholic liver disease, is characterized by triglyceride deposition in hepatocytes, which can advance to steatohepatitis, fibrosis, cirrhosis, and ultimately to hepatocellular carcinoma. In the present work, we studied altered plasma and hepatic lipid metabolome (lipidome) to understand the mechanisms and lipid pattern of early-stage alcohol-induced-fatty liver.Methods: Male Fischer 344 rats were fed 5% alcohol in a Lieber-DeCarli diet. Control rats were pair-fed an equivalent amount of maltose-dextrin. After 1 month, animals were killed and plasma collected. Livers were excised for morphological, immunohistochemical, and biochemical studies. The lipids from plasma and livers were extracted with methyl-tert-butyl ether and analyzed by 750/800 MHz proton nuclear magnetic resonance (1H NMR) and phosphorus (31P) NMR spectroscopy on a 600 MHz spectrometer. The NMR data were then subjected to multivariate statistical analysis.Results: Hematoxylin and Eosin and Oil Red O stained liver sections showed significant fatty infiltration. Immunohistochemical analysis of liver sections from ethanol-fed rats showed no inflammation (absence of CD3 positive cells) or oxidative stress (absence of malondialdehyde reactivity or 4-hydroxynonenal positive staining). Cluster analysis and principal component analysis of 1H NMR data of lipid extracts of both plasma and livers showed a significant difference in the lipid metabolome of ethanol-fed versus control rats. 31P NMR data of liver lipid extracts showed significant changes in phospholipids similar to 1H NMR data. 1H NMR data of plasma and liver reflected several changes, while comparison of 1H NMR and 31P NMR data offered a correlation among the phospholipids.Conclusions: Our results show that alcohol consumption alters metabolism of cholesterol, triglycerides, and phospholipids that could contribute to the development of fatty liver. These studies also indicate that fatty liver precedes oxidative stress and inflammation. The similarities observed in plasma and liver lipid profiles offer a potential methodology for detecting early-stage alcohol-induced fatty liver disease by analyzing the plasma lipid profile.

AB - Background: Hepatic steatosis (fatty liver), an early and reversible stage of alcoholic liver disease, is characterized by triglyceride deposition in hepatocytes, which can advance to steatohepatitis, fibrosis, cirrhosis, and ultimately to hepatocellular carcinoma. In the present work, we studied altered plasma and hepatic lipid metabolome (lipidome) to understand the mechanisms and lipid pattern of early-stage alcohol-induced-fatty liver.Methods: Male Fischer 344 rats were fed 5% alcohol in a Lieber-DeCarli diet. Control rats were pair-fed an equivalent amount of maltose-dextrin. After 1 month, animals were killed and plasma collected. Livers were excised for morphological, immunohistochemical, and biochemical studies. The lipids from plasma and livers were extracted with methyl-tert-butyl ether and analyzed by 750/800 MHz proton nuclear magnetic resonance (1H NMR) and phosphorus (31P) NMR spectroscopy on a 600 MHz spectrometer. The NMR data were then subjected to multivariate statistical analysis.Results: Hematoxylin and Eosin and Oil Red O stained liver sections showed significant fatty infiltration. Immunohistochemical analysis of liver sections from ethanol-fed rats showed no inflammation (absence of CD3 positive cells) or oxidative stress (absence of malondialdehyde reactivity or 4-hydroxynonenal positive staining). Cluster analysis and principal component analysis of 1H NMR data of lipid extracts of both plasma and livers showed a significant difference in the lipid metabolome of ethanol-fed versus control rats. 31P NMR data of liver lipid extracts showed significant changes in phospholipids similar to 1H NMR data. 1H NMR data of plasma and liver reflected several changes, while comparison of 1H NMR and 31P NMR data offered a correlation among the phospholipids.Conclusions: Our results show that alcohol consumption alters metabolism of cholesterol, triglycerides, and phospholipids that could contribute to the development of fatty liver. These studies also indicate that fatty liver precedes oxidative stress and inflammation. The similarities observed in plasma and liver lipid profiles offer a potential methodology for detecting early-stage alcohol-induced fatty liver disease by analyzing the plasma lipid profile.

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