| Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. | |
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MedLine Citation:
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PMID: 17690174 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. OSA is associated with nonalcoholic steatohepatitis (NASH) in obese individuals and may contribute to progression of nonalcoholic fatty liver disease from steatosis to NASH. The purpose of this study was to examine whether CIH induces inflammatory changes in the liver in mice with diet-induced hepatic steatosis. C57BL/6J mice (n = 8) on a high-fat, high-cholesterol diet were exposed to CIH for 6 mo and were compared with mice on the same diet exposed to intermittent air (control; n = 8). CIH caused liver injury with an increase in serum ALT (461 +/- 58 U/l vs. 103 +/- 16 U/l in the control group; P < 0.01) and AST (637 +/- 37 U/l vs. 175 +/- 13 U/l in the control group; P < 0.001), whereas alkaline phosphatase and total bilirubin levels were unchanged. Histology revealed hepatic steatosis in both groups, with mild accentuation of fat staining in the zone 3 hepatocytes in mice exposed to CIH. Animals exposed to CIH exhibited lobular inflammation and fibrosis in the liver, which were not evident in control mice. CIH caused significant increases in lipid peroxidation in serum and liver tissue; significant increases in hepatic levels of myeloperoxidase and proinflammatory cytokines IL-1beta, IL-6, and CXC chemokine MIP-2; a trend toward an increase in TNF-alpha; and an increase in alpha1(I)-collagen mRNA. We conclude that CIH induces lipid peroxidation and inflammation in the livers of mice on a high-fat, high-cholesterol diet. |
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Authors:
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Vladimir Savransky; Shannon Bevans; Ashika Nanayakkara; Jianguo Li; Philip L Smith; Michael S Torbenson; Vsevolod Y Polotsky |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-08-09 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 293 ISSN: 0193-1857 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-10-08 Completed Date: 2007-11-28 Revised Date: 2008-02-14 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G871-7 Citation Subset: IM |
Affiliation:
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Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / complications, physiopathology* Chemokine CXCL2 / blood Cytokines / blood Dietary Fats / administration & dosage* Disease Models, Animal Fatty Liver / complications* Glucose / metabolism Hepatitis / etiology* Lipid Metabolism Male Mice Mice, Inbred C57BL Oxidative Stress Sleep Apnea, Obstructive / physiopathology |
| Grant Support | |
ID/Acronym/Agency:
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DA-16370/DA/NIDA NIH HHS; DK-72488/DK/NIDDK NIH HHS; HL-68715/HL/NHLBI NIH HHS; HL-79554/HL/NHLBI NIH HHS; HL-80105/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CXCL2; 0/Cxcl2 protein, mouse; 0/Cytokines; 0/Dietary Fats; 50-99-7/Glucose |
| Comments/Corrections | |
Comment In:
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Ann Hepatol. 2007 Oct-Dec;6(4):281-3
[PMID:
18007563
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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