Abstract | BACKGROUND & AIMS: METHODS:
Arginase 2-knockout (Arg2(-/-)) mice were studied for changes in liver histology and metabolic phenotype at baseline and after a short term course (7 week) feeding with a high fat (HFAT) diet. In additional experiments, Arg2(-/-) mice received tail vein injections of liposome-encapsulated clodronate (CLOD) over a three-week period to selectively deplete liver macrophages. RESULTS: Unexpectedly, Arg2(-/-) mice showed profound changes in their livers at baseline, characterized by significant steatosis as demonstrated with histological and biochemical analysis. These changes were independent of systemic metabolic parameters and associated with marked mRNA level increases of genes involved in hepatic de novo lipogenesis. Liver injury and inflammation were present with elevated serum ALT, marked infiltration of F4/80 positive cells, and increased mRNA levels of inflammatory genes. HFAT feeding exacerbated these changes. Macrophage depletion after CLOD injection significantly attenuated lipid deposition and normalized lipogenic mRNA profile of livers from Arg2(-/-) mice. CONCLUSIONS: This study identifies arginase 2 as a novel link between innate immune responses, hepatic lipid deposition, and liver injury.
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Authors | Laura A Navarro, Alexander Wree, Davide Povero, Michael P Berk, Akiko Eguchi, Sudakshina Ghosh, Bettina G Papouchado, Serpil C Erzurum, Ariel E Feldstein |
Journal | Journal of hepatology
(J Hepatol)
Vol. 62
Issue 2
Pg. 412-20
(Feb 2015)
ISSN: 1600-0641 [Electronic] Netherlands |
PMID | 25234945
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Arg2 protein, mouse
- Arginase
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Topics |
- Animals
- Arginase
(metabolism)
- Disease Models, Animal
- Fatty Liver
(etiology, immunology, metabolism)
- Hyperargininemia
(complications, immunology, metabolism)
- Immunity, Innate
- Immunoblotting
- Kupffer Cells
(immunology, metabolism)
- Lipid Metabolism
- Lipogenesis
(immunology)
- Liver
(metabolism, pathology)
- Male
- Mice
- Mice, Inbred C57BL
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