title: Fatty acids and hypoxia stimulate the expression and secretion of the adipokine ANGPTL4 (angiopoietin-like protein 4/ fasting-induced adipose factor) by human adipocytes.
abstract: OBJECTIVE
  Hypoxia occurs in white adipose tissue in obesity, modulating the expression and release of specific inflammation-related adipokines. ANGPTL4 (angiopoietin-like protein 4/fasting-induced adipose factor), which is implicated in angiogenesis, lipid metabolism and glucose homeostasis, is a major hypoxia-sensitive gene; recent studies indicate that ANGPTL4 expression is also regulated by fatty acids. We have examined the effects of hypoxia and fatty acids, alone and together, on the expression and release of ANGPTL4 by human adipocytes.
  
  
  METHODS
  Human adipocytes were differentiated and incubated with fatty acids (250 μM) in normoxia (21% O(2)) or hypoxia (1% O(2)). ANGPTL4 mRNA was measured by real-time PCR and the protein in the medium determined by ELISA.
  
  
  RESULTS
  In normoxia, ANGPTL4 gene expression was upregulated by palmitic, oleic, arachidonic and eicosapentaenoic acids, and ANGPTL4 release was increased. In contrast, there was no effect of lauric or myristic acids. Hypoxia alone increased the expression and secretion of ANGPTL4, and lauric, myristic, arachidonic and eicosapentaenoic acids each further increased expression and release in hypoxic adipocytes.
  
  
  CONCLUSIONS
  The expression and secretion of ANGPTL4 by human adipocytes is upregulated by both hypoxia and fatty acids. The stimulatory effect of fatty acids on ANGPTL4 production is augmented under hypoxic conditions.
authors.affiliation: Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, UK.
authors.forename: Pedro
authors.initials: P
authors.lastname: González-Muniesa
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Oliveira
authors.forename: Fátima
authors.initials: F
authors.lastname: Pérez de Heredia
authors.forename: Mary P
authors.initials: MP
authors.lastname: Thompson
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D005227:Fatty Acids; D012333:RNA, Messenger