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

Zinc transporter ZIP12 maintains zinc homeostasis and protects spermatogonia from oxidative stress during spermatogenesis

“…Previous studies reported that zinc contents in the skin, muscle, and bone is reduced in obese mice [ 49 ], and serum zinc concentration is significantly lower in obese children than that in matched normal-weight children [ 50 – 52 ]. Meanwhile, the expressions of some zinc transporters, such as ZNT1 and ZNT6 in brain [ 53 ], ZIP14 in adipose [ 54 , 55 ], and ZnT4, ZnT5, ZnT9, ZIP1, ZIP4 and ZIP6 in leukocyte [ 56 ], were inversely correlated with obesity. Herein, our study provided similar evidence that ZIP12 expression in testis significantly decreased in obese mice, which is associated with reduced sperm zinc content, high sperm ROS level, poor sperm quality and male subfertility.…”

Association of serum levels of vascular endothelial growth factor and thrombospondin-1 to body mass index in polycystic ovary syndrome: a case-control study

“…The subjects in the study were 80 women, aged 15–45 years, from the South Khorasan province of Birjand. The sample size was estimated to be 19.3 persons based on the formula for comparing 2 means, and the results of the Maxwell study and the homeostasis model assessment (HOMA) index with S1=0.6, S2=1.8, d=1.4, α=0.05 and β=0.1, in which 20 women in each group were considered [17].…”

Zinc Transporter ZIP12 Maintains Zinc Homeostasis and Protects Spermatogonia From Oxidative Stress During Spermatogenesis

“…Previous studies reported that zinc contents in the skin, muscle, and bone were reduced in obese mice [49], and serum zinc concentration was signi cantly lower in obese children than that in matched normal-weight children [50][51][52]. Meanwhile, the expressions of some zinc transports, such as ZNT1 and ZNT6 in brain [53], ZIP14 in adipose [54,55], and ZnT4, ZnT5, ZnT9, ZIP1, ZIP4 and ZIP6 in leukocyte [56], were inversely correlated with obesity. Herein, our study provided similar evidence that ZIP12 expression in testis signi cantly decreased in obese mice, which was associated with reduced sperm zinc content, high sperm ROS level, poor sperm quality and male subfertility.…”