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Serum lipoprotein-derived fatty acids regulate hypoxia-inducible factor.
Shao, Wei; Hwang, Jiwon; Liu, Chune; Mukhopadhyay, Debaditya; Zhao, Shan; Shen, Meng-Chieh; Selen, Ebru S; Wolfgang, Michael J; Farber, Steven A; Espenshade, Peter J.
Affiliation
  • Shao W; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Hwang J; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Liu C; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Mukhopadhyay D; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Zhao S; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Shen MC; Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland, USA.
  • Selen ES; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Wolfgang MJ; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Farber SA; Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland, USA.
  • Espenshade PJ; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address: peter.espenshade@jhmi.edu.
J Biol Chem ; 295(52): 18284-18300, 2020 12 25.
Article de En | MEDLINE | ID: mdl-33109611
Oxygen regulates hypoxia-inducible factor (HIF) transcription factors to control cell metabolism, erythrogenesis, and angiogenesis. Whereas much has been elucidated about how oxygen regulates HIF, whether lipids affect HIF activity is un-known. Here, using cultured cells and two animal models, we demonstrate that lipoprotein-derived fatty acids are an independent regulator of HIF. Decreasing extracellular lipid supply inhibited HIF prolyl hydroxylation, leading to accumulation of the HIFα subunit of these heterodimeric transcription factors comparable with hypoxia with activation of downstream target genes. The addition of fatty acids to culture medium suppressed this signal, which required an intact mitochondrial respiratory chain. Mechanistically, fatty acids and oxygen are distinct signals integrated to control HIF activity. Finally, we observed lipid signaling to HIF and changes in target gene expression in developing zebrafish and adult mice, and this pathway operates in cancer cells from a range of tissues. This study identifies fatty acids as a physiological modulator of HIF, defining a mechanism for lipoprotein regulation that functions in parallel to oxygen.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Oxygène / Régulation de l'expression des gènes / Sous-unité alpha du facteur-1 induit par l'hypoxie / Acides gras / Lipoprotéines Type d'étude: Prognostic_studies Limites: Animals / Humans / Male Langue: En Journal: J Biol Chem Année: 2020 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: États-Unis d'Amérique

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Oxygène / Régulation de l'expression des gènes / Sous-unité alpha du facteur-1 induit par l'hypoxie / Acides gras / Lipoprotéines Type d'étude: Prognostic_studies Limites: Animals / Humans / Male Langue: En Journal: J Biol Chem Année: 2020 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: États-Unis d'Amérique