title: Expression Patterns and Correlations with Metabolic Markers of Zinc TransportersZIP14andZNT1in Obesity and Polycystic Ovary Syndrome.
abstract: Polycystic ovary syndrome (PCOS) is associated with infertility, increased androgen levels, and insulin resistance. In adipose tissue, zinc facilitates insulin signaling. Circulating zinc levels are altered in obesity, diabetes, and PCOS; and zinc supplementation can ameliorate metabolic disturbances in PCOS. In adipose tissue, expression of zinc influx transporterZIP14varies with body mass index (BMI), clinical markers of metabolic syndrome, andperoxisome proliferator-activated receptor gamma(PPARG). In this study, we investigated expression levels ofZIP14andPPARGin subcutaneous adipose tissue of 36 PCOS women (17 lean and 19 obese women) compared with 23 healthy controls (7 lean and 16 obese women). Further, expression levels of zinc transporterZIP9, a recently identified androgen receptor, and zinc efflux transporterZNT1were investigated, alongside lipid profile and markers of glucose metabolism [insulin degrading enzyme, retinol-binding protein 4 (RBP4), and glucose transporter 4 (GLUT4)]. We find thatZIP14expression is reduced in obesity and positively correlates withPPARGexpression, which is downregulated with increasing BMI.ZNT1is upregulated in obesity, and bothZIP14andZNT1expression significantly correlates with clinical markers of altered glucose metabolism. In addition,RBP4andGLUT4associate with obesity, but an association with PCOS as such was present only forPPARGandRBP4.ZIP14andZNT1does not relate to clinical androgen status andZIP9is unaffected by all parameters investigated. In conclusion, our findings support the existence of a zinc dyshomeostasis in adipose tissue in metabolic disturbances including PCOS-related obesity.
authors.affiliation: Faculty of Health, Department of Biomedicine, Aarhus University , Aarhus , Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Maxel
authors.affiliation: Department of Obstetrics and Gynecology, Herlev University Hospital , Herlev , Denmark.
authors.forename: Pernille Fog
authors.initials: PF
authors.lastname: Svendsen
authors.affiliation: Faculty of Health, Department of Clinical Medicine, Aarhus University , Aarhus , Denmark.
authors.forename: Kamille
authors.initials: K
authors.lastname: Smidt
authors.affiliation: Faculty of Health, Department of Biomedicine, Aarhus University , Aarhus , Denmark.
authors.forename: Jesper Krogh
authors.initials: JK
authors.lastname: Lauridsen
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
authors.affiliation: Faculty of Health, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Endocrinology (MEA), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Steen Bønlykke
authors.initials: SB
authors.lastname: Pedersen
authors.affiliation: Center for Diabetes Research, Department of Medicine, Gentofte University Hospital , Hellerup , Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
authors.affiliation: Faculty of Health, Department of Biomedicine, Aarhus University , Aarhus , Denmark.
authors.forename: Agnete
authors.initials: A
authors.lastname: Larsen
keywords: Slc30a; Slc39a; ZIP14; ZNT1; obesity; peroxisome proliferator-activated receptor gamma; polycystic ovary syndrome; zinc