title: Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen signaling.
abstract: OBJECTIVE
  The synthetic retinoid fenretinide (FEN) inhibits adiposity in male mice fed a high-fat diet (HFD) in association with alterations in retinoic acid (RA) signaling. Young female mice are protected from obesity via estrogen signaling. We, therefore, investigated whether FEN also influences adiposity in aged female mice differing in parity and whether such effects are mediated by retinoid and estrogen signaling.
  
  
  METHODS
  Aged nulliparous and parous female mice were maintained on HFD ± FEN, and adiposity was assessed. Quantitative polymerase chain reaction was performed on white adipose tissue (WAT), liver, and 3T3-L1 adipocytes treated with RA or FEN ± estrogen.
  
  
  RESULTS
  Parous females were more obese than nulliparous mice independent of age. FEN-HFD prevented the HFD-induced increase in adiposity and leptin levels independently of parity. FEN-HFD induced retinoid-responsive genes in WAT and liver. Parous females had reduced expression of hepatic estrogen-responsive genes, but FEN-HFD up-regulated WAT Cyp19a1 and Esr2 in parous mice. Estrogen and RA acted synergistically to increase RA receptor-mediated gene expression in 3T3-L1 adipocytes. FEN increased Cyp19a1 and Esr2, similar to our findings in vivo.
  
  
  CONCLUSIONS
  The prevention of adiposity by FEN in response to HFD in female mice seems to involve increased retinoid signaling in association with induction of local estrogen production and estrogen signaling in WAT.
authors.affiliation: Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill Health Campus, Aberdeen, Scotland, UK.
authors.forename: Kirsty D
authors.initials: KD
authors.lastname: Shearer
authors.affiliation: Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill Health Campus, Aberdeen, Scotland, UK.|Centre for Genome-Enabled Biology and Medicine, University of Aberdeen, Aberdeen, Scotland, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Morrice
authors.affiliation: Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill Health Campus, Aberdeen, Scotland, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Henderson
authors.affiliation: Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill Health Campus, Aberdeen, Scotland, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Reekie
authors.affiliation: Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill Health Campus, Aberdeen, Scotland, UK.
authors.forename: George D
authors.initials: GD
authors.lastname: Mcilroy
authors.affiliation: Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill Health Campus, Aberdeen, Scotland, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCaffery
authors.affiliation: Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill Health Campus, Aberdeen, Scotland, UK.
authors.forename: Mirela
authors.initials: M
authors.lastname: Delibegovic
authors.affiliation: Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill Health Campus, Aberdeen, Scotland, UK.
authors.forename: Nimesh
authors.initials: N
authors.lastname: Mody
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D059305:Diet, High-Fat; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D017313:Fenretinide / Q000032:analysis / Q000627:therapeutic use*; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004967:Estrogens; D020738:Leptin; D012176:Retinoids; D017313:Fenretinide