High-fat diet aggravates 2,2′,4,4′-tetrabromodiphenyl ether-inhibited testosterone production via DAX-1 in Leydig cells in rats
Authors: Shou-Lin Wang
Chao Wang
Lu Yang
Zhan Zhang
Hengsen Xu
Huibin Dong
Yongquan Yu
Minghui Ji
Jiansheng Zhu
Jun Gu
Journal: Toxicology and Applied Pharmacology (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 2,2′,4,4′-tetrabromodiphenyl ether; DAX-1; High-fat diet; Insulin; Primary Leydig cells
Affiliations: State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China; Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China., Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China., Changzhou Center for Disease Control and Prevention, 203 Taishan Road, Changzhou 2013022, PR China., State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China; Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China. Electronic address: .

Abstract:  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. 

Retracted: No

PubPeer comments:
 Two images in Figure 3B appear to overlap. *** ![file] , 
 Dear Actinoployspora Biskrensis, Thank you very much for pointing out the error that two images in Figure 3B appear to be overlapped in our manuscript published on Toxicol Appl Pharmacol. 2017 May 15;323:1-8. We checked the original pathological images carefully, and found that we initially named the captured images only as u201cnumber-magnificationu201d (i.g. 12-400X) in different groups, but there were the rats that happened to be labeled the same serial number (No. 12) in both ND-BDE47-20 mg kg d group and HFD-BDE47-0.03 mg kg d group, which made the mistake that one of the images for ND-BDE47-20 mg kg d group was carelessly applied for the HFD-BDE47-0.03 mg kg d group. Fortunately, the mistake did not change the conclusions of the manuscript. We are sorry for the late response because we were just told the message for the mistake this week. We now correct the Figure 3B below, and we will contact the journal editors to correct it as soon as possible. Thanks again for your help on our work. Sincerely Shou-Lin Wang ![file] ,