AUTHOR=Maxel Trine , Svendsen Pernille Fog , Smidt Kamille , Lauridsen Jesper Krogh , Brock Birgitte , Pedersen Steen Bønlykke , Rungby Jørgen , Larsen Agnete 

TITLE=Expression Patterns and Correlations with Metabolic Markers of Zinc Transporters ZIP14 and ZNT1 in Obesity and Polycystic Ovary Syndrome

JOURNAL=Frontiers in Endocrinology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2017.00038

DOI=10.3389/fendo.2017.00038

ISSN=1664-2392

ABSTRACT=<p>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 transporter <italic>ZIP14</italic> varies with body mass index (BMI), clinical markers of metabolic syndrome, and <italic>peroxisome proliferator-activated receptor gamma</italic> (<italic>PPARG</italic>). In this study, we investigated expression levels of <italic>ZIP14</italic> and <italic>PPARG</italic> in 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 transporter <italic>ZIP9</italic>, a recently identified androgen receptor, and zinc efflux transporter <italic>ZNT1</italic> were investigated, alongside lipid profile and markers of glucose metabolism [insulin degrading enzyme, retinol-binding protein 4 (<italic>RBP4</italic>), and glucose transporter 4 (<italic>GLUT4</italic>)]. We find that <italic>ZIP14</italic> expression is reduced in obesity and positively correlates with <italic>PPARG</italic> expression, which is downregulated with increasing BMI. <italic>ZNT1</italic> is upregulated in obesity, and both <italic>ZIP14</italic> and <italic>ZNT1</italic> expression significantly correlates with clinical markers of altered glucose metabolism. In addition, <italic>RBP4</italic> and <italic>GLUT4</italic> associate with obesity, but an association with PCOS as such was present only for <italic>PPARG</italic> and <italic>RBP4</italic>. <italic>ZIP14</italic> and <italic>ZNT1</italic> does not relate to clinical androgen status and <italic>ZIP9</italic> is 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.</p>