Hypoxia-inducible factor prolyl hydroxylase 1 (PHD1) deficiency promotes hepatic steatosis and liver-specific insulin resistance in mice
Open accessAbstract
Obesity is associated with local tissue hypoxia and elevated hypoxia-inducible factor 1 alpha (HIF-1α) in metabolic tissues. Prolyl hydroxylases (PHDs) play an important role in regulating HIF-α isoform stability. In the present study, we investigated the consequence of whole-body PHD1 gene (Egln2) inactivation on metabolic homeostasis in mice. At baseline, PHD1-/- mice exhibited higher white adipose tissue (WAT) mass, despite lower body weight, and impaired insulin sensitivity and glucose tolerance when compared to age-matched wild-type (WT) mice. When fed a synthetic low-fat diet, PHD1-/- mice also exhibit a higher body weight gain and WAT mass along with glucose intolerance and systemic insulin resistance compared to WT mice. PHD1 deficiency led to increase in glycolytic gene expression, lipogenic proteins ACC and FAS, hepatic steatosis and liver-specific insulin resistance. Furthermore, gene markers of inflammation were also increased in the liver, but not in WAT or skeletal muscle, of PHD1-/- mice. As expected, high-fat diet (HFD) promoted obesity, hepatic steatosis, tissue-specific inflammation and systemic insulin resistance in WT mice but these diet-induced metabolic alterations were not exacerbated in PHD1-/- mice. In conclusion, PHD1 deficiency promotes hepatic steatosis and liver-specific insulin resistance but does not worsen the deleterious effects of HFD on metabolic homeostasis.
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PHD1 knockout mice have greater fat pad mass and impaired glucose tolerance but do not show exacerbated diet-induced metabolic changes compared with wild-type mice.
“PHD1 KO mice exhibit a greater fat pad mass and impaired glucose tolerance but do not show exacerbated diet-induced metabolic changes compared with WT mice (6).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [6]
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Self-citation
- Authors
- Thomas, A., Belaidi, E., Aron-Wisnewsky, J., van der Zon, G. C., Levy, P., Clement, K., Pepin, J.-L., Godin-Ribuot, D., & Guigas, B.
- Affiliations
- Inserm (FR)
- Leiden University Medical Center (NL)
- Corresponding author
- Guigas, Bruno
- Venue
- Scientific Reports
- Published
- 2016-04-20
- Volume
- 6
- Issue
- 1
- Pages
- 24618-24618
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4837354
- OpenAlex
- W2340727889
- Cited by
- 33
- References
- 45
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 1
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion, cc-by)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- Fondation du Souffle
- Fondation de France
- Agir pour les Maladies Chroniques
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- PHD1, EGLN2, hypoxia-inducible factor-1α, hepatic steatosis, obesity, impaired glucose tolerance, tissue hypoxia, liver inflammation, high-fat diet, metabolic homeostasis, lipogenesis, glycolysis
- MeSH terms
- Animals, Body Weight, Disease Models, Animal, Energy Metabolism, Fatty Liver, Homeostasis, Inflammation, Insulin Resistance, Male, Organ Specificity, Procollagen-Proline Dioxygenase, Glucose Intolerance, Mice, Knockout, Adiposity, Dyslipidemias, Mice, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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