Phagocytic function of Kupffer cells in mouse nonalcoholic fatty liver disease models: Evaluation with superparamagnetic iron oxide.

Abstract

PURPOSE:

To evaluate the Kupffer cell (KC) phagocytic function using superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) in animal models with nonalcoholic fatty liver disease (NAFLD).

MATERIALS AND METHODS:

Mouse NAFLD models with varying severity were created by feeding high-fat, high-cholesterol (HFHC) diets to ob/ob mice for 3, 6, or 12 weeks. SPIO-MRI was performed on a 4.7-T animal scanner in the mouse NAFLD models, in wildtype control mouse, and in the NAFLD mice (NAFLD treatment group) that received 6 weeks of pioglitazone treatment. The relative signal loss (RSL) of the liver was measured in each animal to represent the magnitude of SPIO-induced signal loss of the liver. Liver samples were analyzed for steatosis, inflammation, fibrosis, and the number of SPIO particles and KCs.

RESULTS:

RSL values of the NAFLD mice (range of RSL value, 26.3%-53.8%) seen on SPIO-MRI were significantly lower than those of the control mice (67.7%-74.8%, P ≤ 0.008) and decreased in proportion to the duration of their HFHC diet (mean ± SD, 53.7% ± 10.9, 44.7% ± 8.2, and 26.3% ± 12.6, after 3-, 6-, and 12-week HFHC diet, respectively, on 20-minute delayed images). For the NAFLD treatment group, the RSL values increased after 6 weeks of pioglitazone treatment, compared with the values before treatment (P ≤ 0.039). The RSL values had significant independent correlation with both hepatic steatosis (P = 0.007) and inflammation (P = 0.023).

CONCLUSION:

KC phagocytic dysfunction is aggravated in the progression of NAFLD and may be reversible with therapeutic intervention. SPIO-MRI may be useful for classifying the severity of NAFLD and monitoring the treatment response of NAFLD.

• Authors: Hyunhee Cheong, Seung Soo Lee, Jin Seong Lee, Jihoon Kim, Seong Who Kim, Woo Je Lee
• Journal: Journal of magnetic resonance imaging : JMRI (J Magn Reson Imaging) Vol. 41 Issue 5 Pg. 1218-27 (May 2015) ISSN: 1522-2586 [Electronic] United States
• PMID: 24916329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Contrast Media
• Dextrans
• Magnetite Nanoparticles
• ferumoxtran-10

Topics

• Animals
• Contrast Media
• Dextrans
• Image Enhancement (methods)
• Image Interpretation, Computer-Assisted (methods)
• Kupffer Cells (pathology)
• Magnetic Resonance Imaging (methods)
• Magnetite Nanoparticles
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (pathology, physiopathology)
• Phagocytosis
• Reproducibility of Results
• Sensitivity and Specificity