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Hepatocyte HIF-1 and Intermittent Hypoxia Independently Impact Liver Fibrosis in Murine NAFLD

Am J Respir Cell Mol Biol. 2021-05; 
Omar A Mesarwi, Esteban A Moya, Xin Zhen, Mary Gautane, Huyai Zhao, Paula Wegbrans Giró, Mouza Alshebli, Kendall E McCarley, Ellen C Breen, Atul Malhotra
Products/Services Used Details Operation
Custom DNA/RNA Oligos … injected intraperitoneally with antisense oligonucleotide (ASO) targeting HIF-1α (30 mg/kg in 100 µL phosphate buffered saline [PBS], GenScript Biotech, Piscataway, NJ) twice a week for the final six weeks of the experiment (ie, during the entire duration of IH exposure) … Get A Quote

摘要

Obstructive sleep apnea (OSA) is associated with insulin resistance, lipid dysregulation, and hepatic steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD). We have previously shown that hepatocyte hypoxia inducible factor-1 (HIF-1) mediates the development of liver fibrosis in a mouse model of NAFLD. We hypothesized that intermittent hypoxia (IH) modeling OSA would worsen hepatic steatosis and fibrosis in murine NAFLD, via HIF-1. Mice with hepatocyte-specific deletion of Hif1a () and wild-type () controls were fed a high -fat diet to induce NAFLD with steatohepatitis. Half from each group were exposed to IH, and the other half to intermittent air. Glucose tolerance test was performed prior to sacr... More

关键词

HIF-1, OSA, hepatic fibrosis, hyperglycemia, lipid metabolism