ArticleMolecular and cellular biology2014
Loss of von Hippel-Lindau protein (VHL) increases systemic cholesterol levels through targeting hypoxia-inducible factor 2α and regulation of bile acid homeostasis.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease.American journal of nephrology · 2017Trial
- Microglial cholesterol reprogramming drives cognitive impairment under hypobaric hypoxia.Journal of neuroinflammation · 2026Article
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Review
- Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.International journal of molecular sciences · 2024Article
- Hypoxia-Induced Signaling in Gut and Liver Pathobiology.Annual review of pathology · 2024Review
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Preliminary screening of biomarkers in HAPE based on quasi-targeted metabolomics.Frontiers in physiology · 2023Article
- Article
- Whole-Body Prolyl Hydroxylase Domain (PHD) 3 Deficiency Increased Plasma Lipids and Hematocrit Without Impacting Plaque Size in Low-Density Lipoprotein Receptor Knockout Mice.Frontiers in cell and developmental biology · 2021Article
- Hepatic metabolic regulation by nuclear factor E4BP4.Journal of molecular endocrinology · 2021Review
- Turning the Oxygen Dial: Balancing the Highs and Lows.Trends in cell biology · 2020Review
- Two-stage metabolic remodelling in macrophages in response to lipopolysaccharide and interferon-γ stimulation.Nature metabolism · 2019Article
- The Evolution of Cholesterol-Rich Membrane in Oxygen Adaption: The Respiratory System as a Model.Frontiers in physiology · 2019Review
- Knockout of microRNA-21 attenuates alcoholic hepatitis through the VHL/NF-κB signaling pathway in hepatic stellate cells.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Metabolic Profiling of the Novel Hypoxia-Inducible Factor 2Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- A central role for hypoxia-inducible factor (HIF)-2α in hepatic glucose homeostasis.Nutrition and healthy aging · 2017Review
- Article
- Hypoxia-inducible factor/MAZ-dependent induction of caveolin-1 regulates colon permeability through suppression of occludin, leading to hypoxia-induced inflammation.Molecular and cellular biology · 2014Article
- Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Cholesterol synthesis is a highly oxygen-dependent process. Paradoxically, hypoxia is correlated with an increase in cellular and systemic cholesterol levels and risk of cardiovascular diseases. The mechanism for the increase in cholesterol during hypoxia is unclear. Hypoxia signaling is mediated through hypoxia-inducible factor 1α (HIF-1α) and HIF-2α. The present study demonstrates that activation of HIF signaling in the liver increases hepatic and systemic cholesterol levels due to a decrease in the expression of cholesterol hydroxylase CYP7A1 and other enzymes involved in bile acid synthesis. Specifically, activation of hepatic HIF-2α (but not HIF-1α) led to hypercholesterolemia. HIF-2α repressed the circadian expression of Rev-erbα, resulting in increased expression of E4BP4, a negative regulator of Cyp7a1. To understand if HIF-mediated decrease in bile acid synthesis is a physiologically relevant pathway by which hypoxia maintains or increases systemic cholesterol levels, two hypoxic mouse models were assessed, an acute lung injury model and mice exposed to 10% O2 for 3 weeks. In both models, cholesterol levels increased with a concomitant decrease in expression of genes involved in bile acid synthesis. The present study demonstrates that hypoxic activation of hepatic HIF-2α leads to an adaptive increase in cholesterol levels through inhibition of bile acid synthesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.