title: Gene expression of the zinc transporter ZIP14 (SLC39a14) is affected by weight loss and metabolic status and associates with PPARγ in human adipose tissue and 3T3-L1 pre-adipocytes.
abstract: BACKGROUND
  The expansion and function of adipose tissue are important during the development of insulin resistance and inflammation in obesity. Zinc dyshomeostasis is common in obese individuals. In the liver, zinc influx transporter ZIP14, affects proliferation and glucose metabolism but the role of ZIP14 in adipose tissue is still unknown. This study investigates ZIP14 gene expression in human adipose tissue before and after weight loss as well as the regulation of ZIP14 during early adipogenesis.
  
  
  METHODS
  Fourteen obese individuals were investigated before and after a 10 week weight loss intervention and compared to 14 non-obese controls. Gene expressions of ZIP14 and peroxisome proliferator-activated receptor γ (PPARγ) were measured in subcutaneous adipose tissue and correlated with metabolic and inflammatory markers. Further, we investigated gene expression of ZIP14 and PPARγ during early adipogenesis of 3T3-L1 pre-adipocytes, together with an in silico analysis of PPARγ binding motifs in the promoter sequence of ZIP14.
  
  
  RESULTS
  ZIP14 was down-regulated in obese individuals compared to non-obese controls (p = 0.0007) and was up-regulated after weight loss (p = 0.0005). Several metabolic markers of clinical importance, including body mass index, triglyceride, and insulin resistance, were inversely correlated with ZIP14. During early adipogensis an up-regulation of ZIP14 gene expression was found. PPARγ gene expression was positively correlated with the ZIP14 gene expression in both adipose tissue and during adipogenesis. However, in silico analysis revealed that the ZIP14 promoter does not contain PPARγ-binding motifs.
  
  
  CONCLUSIONS
  We hypothesize that ZIP14-mediated zinc influx might directly influence PPARγ activity and that ZIP14 may regulate expansion and function of adipose tissue and serve as a potential biomarker for metabolic stress.
authors.affiliation: Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Maxel
authors.affiliation: Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark ; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Kamille
authors.initials: K
authors.lastname: Smidt
authors.affiliation: Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Agnete
authors.initials: A
authors.lastname: Larsen
authors.affiliation: Department of Endocrinology (MEA), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Bennetzen
authors.affiliation: Department of Endocrinology (MEA), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Karina
authors.initials: K
authors.lastname: Cullberg
authors.affiliation: Department of Endocrinology (MEA), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Fjeldborg
authors.affiliation: Department of Endocrinology (MEA), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
authors.affiliation: Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark ; Department of Endocrinology (MEA), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.affiliation: Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark ; Department of Medicine, Center for Diabetes Research, Gentofte University Hospital, Hellerup, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
keywords: Adipogenesis; Adipose tissue; Obesity; SLC39a14; ZIP14