In vivo assessment of hepatic triglycerides in murine non-alcoholic fatty liver disease using magnetic resonance spectroscopy |
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Authors: | Ian R. Corbin Emma E. Furth Stephen Pickup Evan S. Siegelman Edward J. Delikatny |
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Affiliation: | 1. Department of Radiology, University of Pennsylvania School of Medicine, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA;2. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA |
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Abstract: | In vivo1H 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 vivo1H MRS may be a suitable method to monitor the progression of steatohepatitis. |
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Keywords: | CHESS, Chemical Shift Selective (water suppression) FOV, field of view i.p., intraperitoneal LPS, lipopolysaccharide MCDD, methionine&ndash choline deficient diet MRS, magnetic resonance spectroscopy NAFLD, non-alcoholic fatty liver disease NASH, non-alcoholic steatohepatitis NMR, nuclear magnetic resonance ob/ob, leptin-deficient obese mice PLA2, phospholipase A2 PRESS, point resolved spectroscopy NT, Number of transients TE, echo time TM, mixing time TR, repetition time TNF, tumor necrosis factor |
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