High-fat diet aggravates 2,2′,4,4′-tetrabromodiphenyl ether-inhibited testosterone production via DAX-1 in Leydig cells in rats
Journal Article
·
· Toxicology and Applied Pharmacology
- State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China)
- Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China)
- Changzhou Center for Disease Control and Prevention, 203 Taishan Road, Changzhou 2013022 (China)
Growing evidence has revealed that a high-fat diet (HFD) could lead to disorders of glycolipid metabolism and insulin-resistant states, and HFDs have been associated with the inhibition of testicular steroidogenesis. Our previous study demonstrated that 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) could increase the risk of diabetes in humans and reduce testosterone production in rats. However, whether the HFD affects BDE47-inhibited testosterone production by elevating insulin levels and inducing related pathways remains unknown. In male rats treated with BDE47 by gavage for 12 weeks, the HFD significantly increased the BDE47 content of the liver and testis and increased the weight of the adipose tissue; increased macrovesicular steatosis in the liver and the levels of triglycerides, fasting glucose and insulin; further aggravated the disruption of the seminiferous epithelium; and lowered the level of testosterone, resulting in fewer sperm in the epididymis. Of note, the HFD enhanced BDE47-induced DAX-1 expression and decreased the expression levels of StAR and 3β-HSD in the testicular interstitial compartments in rats. In isolated primary Leydig cells from rats, BDE47 or insulin increased DAX-1 expression, decreased the expression of StAR and 3β-HSD, and reduced testosterone production, which was nearly reversed by knocking down DAX-1. These results indicated that the HFD aggravates BDE47-inhibited testosterone production through hyperinsulinemia, and the accumulation of testicular BDE47 that induces the up-regulation of DAX-1 and the subsequent down-regulation of steroidogenic proteins, i.e., StAR and 3β-HSD, in Leydig cells. - Highlights: • High-fat diet (HFD) aggravates the accumulation of BDE47 in liver and testis in rats. • HFD aggravates BDE47-inhibited testosterone production via DAX-1 in Leydig cells. • HFD enhances BDE47-induced the disorder of glycolipid metabolism and hyperinsulinemia. • Both hyperinsulinemia and accumulation of BDE47 inhibited testosterone via DAX-1.
- OSTI ID:
- 22690971
- Journal Information:
- Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 323; ISSN TXAPA9; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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