Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1791, Issue 8, Pages 757-763Publisher
ELSEVIER
DOI: 10.1016/j.bbalip.2009.02.014
Keywords
In vivo MR spectroscopy; Fatty liver; Non-alcoholic steatohepatitis; Non-alcoholic fatty liver disease; Ob/ob mice; Methionine-choline deficiency
Funding
- University Research Foundation
- Small Animal Imaging Resource [NIH U24 CA-083105]
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In vivo H-1 magnetic resonance spectroscopy (MRS) was used to examine the progression of fatty liver in two murine models of progressive hepatic steatosis: leptin-deficient obese (ob/ob) mice and mice maintained on a diet deficient in methionine and choline (MCDD). Ob/ob mice displayed high levels of intracellular hepatic triglycerides as early as 9 weeks after birth, as observed with MRS and histopathology. Single voxel spectra of ob/ob liver displayed strong resonances arising from saturated (1.3 ppm) and unsaturated (2.8 and 5.3 ppm) fatty acyl chains that could be resolved in the absence of water suppression. Hepatic inflammation, induced by lipopolysaccharide administration, led to a significant increase in unsaturated and polyunsaturated fatty acyl chain resonances (P<0.05), indicating a change in the composition of hepatic triglycerides in lipid droplets. Mice maintained on the MCDD displayed histological evidence of hepatic steatosis as early as two weeks, progressing to macrovesicular steatohepatitis at 10 weeks. The histological changes were accompanied by significant increases in saturated and unsaturated fatty acyl chain resonances and a significant decrease in the lipid/(water + lipid) ratio (P<0.05). These results indicate that in vivo H-1 MRS may be a suitable method to monitor the progression of steatohepatitis. (C) 2009 Elsevier B.V. All rights reserved.
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