LIPIDOMICS OF ALCOHOL-INDUCED FATTY LIVER

Harshica Fernando, Ph.D. ¹, S. Kondraganti, M.D. ², K.K. Bhopale, DVM, Ph.D. ¹, M. Neerathilingam, Ph.D. ², D.E. Volk, Ph.D. ², B.S. Kaphalia, Ph.D. ¹, B.A. Luxon, Ph.D. ², P.J. Boor, M.D. ¹, and G.A.S. Ansari, Ph.D. ^{1, 2}

Departments of ¹Pathology and ²Biochemistry and Molecular Biology, UTMB

Background: Hepatic steatosis (fatty liver) is an early and reversible stage of alcoholic liver disease (ALD), which is a major cause of liver-associated illnesses and deaths. Objective: Our objective in this project is to elucidate the mechanism leading to fatty liver and to develop a biomarker signature for the early detection of ALD. Methods: Fischer 344 rats were fed Lieber-DeCarli liquid diet containing 5% alcohol for one month. Control animals were pair-fed with liquid diet containing equivalent calories substituted by maltose-dextrin. After sacrificing the animals, livers were removed, weighed and subjected to morphological and immunohistochemical analysis. Plasma was extracted and analyzed by 750 MHz proton nuclear magnetic resonance (NMR) spectroscopy. Results: The body and liver weights were not significantly changed in ethanol-fed vs. control group. Fatty infiltration was confirmed by H&E and Oil Red O staining of the liver sections of ethanol-fed group. No indication of inflammation or oxidative stress was found in alcohol-fed vs. control group. Cluster analysis and principal component analysis of NMR data of plasma lipids were significantly different for the alcohol-fed group. Conclusions: These studies indicate that fatty liver is an early change that precedes oxidative stress and inflammation, and may be identified by the altered plasma lipid profile.

Supported by NIH grant number R01AA016364.