Serum lipoprotein-derived fatty acids regulate hypoxia-inducible factor.
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.
Mots clés
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