title: All-trans retinoic acid decreases murine adipose retinol binding protein 4 production.
abstract: OBJECTIVE
  Adipose-derived retinol binding protein 4 (RBP4) might contribute to the development of insulin resistance, and therefore further knowledge of factors regulating it is of interest. Retinoic acid, the acid form of vitamin A, affects the expression of several adipokines related to insulin sensitivity in mice. Here, we sought to investigate its impact on adipose RBP4 production.
  
  
  METHODS
  Changes in RBP4 expression were analyzed in adipose tissues and liver of mice treated in vivo with all-trans retinoic acid (ATRA), and in 3T3-L1 adipocytes and adipocytes derived from mouse embryonic fibroblasts exposed to ATRA.
  
  
  RESULTS
  ATRA treatment in mice increased insulin sensitivity as assessed by the homeostatic model assessment for insulin resistance, and led to a reduction of RBP4 mRNA and protein levels in adipose tissues, a reduction of RBP4 protein but not RBP4 mRNA levels in the liver, and a marked increase in circulating RBP4 protein levels. In adipocyte cell models, ATRA down-regulated RBP4 mRNA levels in a dose-dependent manner: this effect was reproduced by retinaldehyde and retinoid receptors agonists, and correlated with a reduced accumulation of RBP4 protein in the culture medium.
  
  
  CONCLUSIONS
  These results reveal a selective effect of ATRA inhibiting RBP4 expression specifically in adipocytes, and reinforce the concept that vitamin A vitamers may affect insulin sensitivity through effects on adipokine production.
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Mercader
authors.forename: Nuria
authors.initials: N
authors.lastname: Granados
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Bonet
authors.forename: Andreu
authors.initials: A
authors.lastname: Palou