ArticleScientific reports2016
Hypoxia-inducible factor prolyl hydroxylase 1 (PHD1) deficiency promotes hepatic steatosis and liver-specific insulin resistance in mice.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 33 citations in OpenAlex.
- PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.Pflugers Archiv : European journal of physiology · 2024Review
- Context-dependent regulation of lipid accumulation in adipocytes by a HIF1α-PPARγ feedback network.Cell systems · 2023Article
- The role of hypoxia-inducible factor 1α in hepatic lipid metabolism.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphorylation.Scientific reports · 2022Article
- Intermittent Hypoxia Rewires the Liver Transcriptome and Fires up Fatty Acids Usage for Mitochondrial Respiration.Frontiers in medicine · 2022Article
- Identification of the hub genes related to adipose tissue metabolism of bovine.Frontiers in veterinary science · 2022Article
- Hypoxia-inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair.The Journal of experimental medicine · 2021Article
- Effects of a novel polyphenol-rich plant extract on body composition, inflammation, insulin sensitivity, and glucose homeostasis in obese mice.International journal of obesity (2005) · 2021Article
- The helminth glycoprotein omega-1 improves metabolic homeostasis in obese mice through type 2 immunity-independent inhibition of food intake.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Hypoxia-inducible factors and diabetes.The Journal of clinical investigation · 2020Review
- PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase.Nature communications · 2020Article
- The Somatotropic Axis in the Sleep Apnea-Obesity Comorbid Duo.Frontiers in endocrinology · 2020Article
- Hypoxia and Non-alcoholic Fatty Liver Disease.Frontiers in medicine · 2020Review
- The PHD1 oxygen sensor in health and disease.The Journal of physiology · 2018Review
- Hypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease.International journal of molecular sciences · 2018Review
- Differences in oxidative metabolism modulation induced by ischemia/reperfusion between trained and untrained individuals assessed by NIRS.Physiological reports · 2017Article
- High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation.Scientific reports · 2017Article
- The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis.The Journal of clinical investigation · 2017Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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