Deoxynivalenol Exposure Suppresses Adipogenesis by Inhibiting the Expression of Peroxisome Proliferator-Activated Receptor Gamma 2 (PPARγ2) in 3T3-L1 Cells.

Ruqin Lin,Yiqun Deng,Shulin Tang,Jikai Wen,Xiaoxuan Chen,Ting Zheng,Jiahui Zhu,Yurong Zhao,Danyang Li

doi:10.3390/ijms21176300

Abstract

Deoxynivalenol (DON)—a type B trichothecene mycotoxin, mainly produced by the secondary metabolism of Fusarium—has toxic effects on animals and humans. Although DON’s toxicity in many organs including the adrenal glands, thymus, stomach, spleen, and colon has been addressed, its effects on adipocytes have not been investigated. In this study, 3T3-L1 cells were chosen as the cell model and treated with less toxic doses of DON (100 ng/mL) for 7 days. An inhibition of adipogenesis and decrease in triglycerides (TGs) were observed. DON exposure significantly downregulated the expression of PPARγ2 and C/EBPα, along with that of other adipogenic marker genes in 3T3-L1 cells and BALB/c mice. The anti-adipogenesis effect of DON and the downregulation of the expression of adipogenic marker genes were effectively reversed by PPARγ2 overexpression. The repression of PPARγ2′s expression is the pivotal event during DON exposure regarding adipogenesis. DON exposure specifically decreased the di-/trimethylation levels of Histone 3 at lysine 4 in 3T3-L1 cells, therefore weakening the enrichment of H3K4me2 and H3K4me3 at the Pparγ2 promoter and suppressing its expression. Conclusively, DON exposure inhibited PPARγ2 expression via decreasing H3K4 methylation, downregulated the expression of PPARγ2-regulated adipogenic marker genes, and consequently suppressed the intermediate and late stages of adipogenesis. Our results broaden the current understanding of DON’s toxic effects and provide a reference for addressing the toxicological mechanism of DON’s interference with lipid homeostasis.

Highlights

Deoxynivalenol (DON), a type B trichothecene mycotoxin, is one of the most polluting mycotoxins, and is mainly produced by Fusarium [1,2]
It is reasonable to consider that a lower intake of food in DON-exposed animal individuals would result in decreased weight gain due to diarrhea and loss of appetite, but it would be interesting to understand whether DON administration could directly inhibit adipogenesis
DON had a dose-dependent, negative effect on both lipid droplets and TG levels. These data suggested that DON inhibited adipogenesis and had an apparent negative impact on 3T3-L1 adipocytes, even at relatively non-toxic concentrations

Summary

Introduction

Deoxynivalenol (DON), a type B trichothecene mycotoxin, is one of the most polluting mycotoxins, and is mainly produced by Fusarium [1,2]. DON, known as “vomitoxin”, causes vomiting in swine [3]. DON has a negative impact on animal health, especially causing gastrointestinal disorders in monogastric animals [4]. Acute exposure to DON leads to vomiting and diarrhea, and is associated with a loss of appetite, while long-term exposure leads to decreased weight gain, intestinal toxicity, cell-mediated immune dysregulation, neurological disorders, lipid peroxidation, and high sensitivity towards disease [5,6,7,8]. It is reasonable to consider that a lower intake of food in DON-exposed animal individuals would result in decreased weight gain due to diarrhea and loss of appetite, but it would be interesting to understand whether DON administration could directly inhibit adipogenesis

Methods

Results

Conclusion