title: Action of nicotinic acid on the reversion of hypoxic-inflammatory link on 3T3-L1 adipocytes.
abstract: BACKGROUND
  Hypoxia resulting from adipocyte expansion is considered the basis of the inflammatory milieu observed in Metabolic Syndrome. Nicotinic acid can act on adipocytes interfering on the inflammatory response. In this study, we investigated the role of HIF-1 α (hypoxia-inducible factor -1 alpha) in the inflammatory process induced by hypoxia. The effect of nicotinic acid on the PPARs (peroxisome proliferator-activated receptors) expression during the inflammatory response was assessed over its action under HIF-1 α in 3T3-L1 adipocytes submitted to hypoxia.
  
  
  METHODS
  3T3-L1 adipocytes were pre-treated with nicotinic acid and incubated under hypoxic conditions. The level of adipokines and HIF-1 α were quantified using immunoassays. Adipokine expression was measured using real-time PCR, whereas PPARs and HIF-1 α expression were analyzed by western blot. The statistical significance of the differences between variables studied was determined by analysis of variance (ANOVA) complemented by Bonferroni's test.
  
  
  RESULTS
  The results demonstrated an increase in leptin and PAI-1 (plasminogen activator inhibitor-1) expression, while adiponectin production decreased under hypoxia. In parallel, induction with hypoxia enhanced HIF-1 α expression, despite causing reduced expression of PPAR α and PPAR γ. However, nicotinic acid reversed adipokine modulation under hypoxic conditions, leading to decreased HIF-1 α expression and increased PPARs expression.
  
  
  CONCLUSIONS
  Our findings suggest that nicotinic acid blunt the inflammatory response resulting from hypoxia by the reduction of HIF-1 α expression and concomitant increase of PPARs α and γ expression in 3T3-L1 adipocytes.
authors.affiliation: Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 781, Vila Clementino, São Paulo, Brazil. renata.nakamichi@bol.com.br.
authors.forename: Renata
authors.initials: R
authors.lastname: Nakamichi
authors.affiliation: Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 781, Vila Clementino, São Paulo, Brazil.
authors.forename: Erika Prates
authors.initials: EP
authors.lastname: Miranda
authors.affiliation: Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 781, Vila Clementino, São Paulo, Brazil.
authors.forename: Sylvia Madeira de Vergueiro
authors.initials: SM
authors.lastname: Lobo
authors.affiliation: Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 781, Vila Clementino, São Paulo, Brazil.
authors.forename: Vivian Regina
authors.initials: VR
authors.lastname: Tristão
authors.affiliation: Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 781, Vila Clementino, São Paulo, Brazil.|Universidade Nove de Julho, São Paulo, Brazil.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Dalboni
authors.affiliation: Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 781, Vila Clementino, São Paulo, Brazil.
authors.forename: Beata Marie Redublo
authors.initials: BM
authors.lastname: Quinto
authors.affiliation: Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 781, Vila Clementino, São Paulo, Brazil.|Dialysis Unit, Intensive Care Center, Hospital Israelita Albert Einstein, São Paulo, Brazil.|Division of Nephrology, Tufts University School of Medicine, Boston, USA.
authors.forename: Marcelo Costa
authors.initials: MC
authors.lastname: Batista
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000378:metabolism; D051379:Mice; D009525:Niacin / Q000494:pharmacology*; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D058258:Serpin E2 / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020738:Leptin; D047493:PPAR alpha; D047495:PPAR gamma; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D009525:Niacin
keywords: Adipocyte; Hypoxia; Inflammation; Nicotinic acid; Obesity