Hypoxia Suppresses High Fat Diet-Induced Steatosis And Development Of Hepatic Adenomas
AuthorSweeney, Nathan W
Gomes, Cecil J
De Armond, Richard
Centuori, Sara M
Martinez, Jesse D
AffiliationUniv Arizona, Dept Med, Div Pulm Allergy Crit Care & Sleep Med, Hlth Sci Ctr Sleep & Circadian Sci
Univ Arizona, Canc Biol Grad Interdisciplinary Program
Univ Arizona, Canc Ctr
Univ Arizona, Dept Cellular & Mol Med Cell & Mol Med
MetadataShow full item record
PublisherDOVE MEDICAL PRESS LTD
CitationSweeney, N. W., Gomes, C. J., De Armond, R., Centuori, S. M., Parthasarathy, S., & Martinez, J. D. Hypoxia Suppresses High Fat Diet-Induced Steatosis And Development Of Hepatic Adenomas.
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AbstractPurpose: Nonalcoholic fatty liver disease (NAFLD) is considered the most common form of silent liver disease in the United States and obesity is associated with increased risk of NAFLD. Obstructive sleep apnea (OSA) which is common in obese individuals is associated with a greater incidence of NAFLD, which in turn, increases the risk for hepatocellular carcinoma (HCC). It is unclear how obesity, OSA and NAFLD interrelate nor how they collectively contribute to an increased risk for developing HCC. Patients and methods: Male BALB/c mice were exposed to diethylnitrosamine and phenobarbital followed by 48 weeks of either standard chow diet (chow), chow with hypoxia, high-fat diet, or a combination of hypoxia and high-fat diet. We noninvasively monitored tumor development using micro-CT imaging. We tracked the total weight gained throughout the study. We evaluated liver histology, fat accumulation, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1-alpha (HIF-1 alpha) expression, as well as, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Results: A high-fat diet without hypoxia led to the development of obesity that induced hepatic steatosis and promoted tumorigenesis. Animals on a high-fat diet and that were also exposed to hypoxia had lower total weight gain, lower steatosis, lower serum AST and ALT levels, and fewer number of hepatic adenomas than a high-fat diet without hypoxia. Conclusion: These findings suggest that hypoxia abrogates obesity, hepatic steatosis, and hepatic tumorigenesis related to a high-fat diet.
NoteOpen access journal
VersionFinal published version
SponsorsNational Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA184920, T32 T32CA009213, T32CA009213-32S1, R01CA129688-03S1]; National Cancer Institute Cancer Center Support GrantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA023074]