Zinc Attenuates Prostate Hyperplasia and Inflammatory Injury in Obese Rats by Regulating Zinc Homeostasis and Inhibiting the JAK1/STAT3 Pathway.

Background: Obesity is an important risk factor for prostate damage. The importance of zinc in male reproductive spermatogenesis and the anti-inflammatory properties of zinc have been studied. However, the role of zinc in obesity-induced prostate proliferation and inflammatory injury and changes in zinc transporters are unknown and require extensive research and validation.

Materials and methods: In this study, we modeled high-fat-fed obese rats. Then, the zinc supplementation group was given daily intragastric administration of zinc sulfate saline solution, while the control group and the high-fat group received the same amount of saline intragastric administration for 8 consecutive weeks. Sperm parameters were statistically analyzed, serum hormones were determined by chemiluminescence immunoanalyzer, and biochemical indexes were determined by automatic biochemical instrument. Inflammatory factors in prostate tissue were evaluated by enzyme-linked immunosorbent assay (ELISA), zinc content in prostate tissue was determined by inductively coupled plasma mass spectrometry (ICP-MS), and zinc transporters, inflammation and apoptosis indicators in prostate tissues were analyzed by Western Blot analysis (WB).

Result: We found that obese rats had decreased sperm motility and sperm count and decreased androgens, leading to male reproductive disorders, whereas sperm motility and sperm count were increased in obese rats after zinc supplementation. The prostate epithelial cells of obese rats showed papillary proliferation with leukocyte infiltration, and the papillary proliferation of epithelial cells was alleviated after zinc supplementation. Meanwhile, pro-inflammatory cytokines and insulin growth factors IL-6, IL-1β, and IGF1 were significantly increased in prostate tissues of obese rats, whereas they were decreased after zinc supplementation. The expression of zinc transporters ZIP10 and ZIP6 was increased and the expression of ZnT3 was decreased in obese rats, while the expression of zinc transporters ZIP6 and ZIP10 was decreased and the expression of ZnT3 was increased after zinc supplementation. WB results showed that zinc supplementation reduced the expression of JAK1/STAT3, elevated the expression of caspase8, caspase3, and Bax, and decreased the expression of Bcl2. Bcl2 expression. This may be due to the fact that zinc supplementation can reduce the level of prostate inflammatory factors and insulin growth factor and promote apoptosis, thus improving prostate cell proliferation and inflammatory injury.

Conclusion: Zinc ameliorates prostate proliferation and inflammatory injury in obese rats by regulating zinc homeostasis, inhibiting the JAK1/STAT3 signaling pathway, and promoting apoptosis. These results provide new insights into the role of zinc as a regulator of prostate metabolism and further illustrate the potential application of zinc in male reproductive disorders.