Zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota

Zearalenone (ZEA), produced by Fusarium, is a fungal toxin commonly found in maize, wheat, and other cereals. ZEA has the ability to bind to estrogen receptors of humans and animals and is an environmental endocrine disruptor that may interfere with glucose homeostasis and lipid metabolism. In this...

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Main Authors: Xiao Han, Bingxin Huangfu, Tongxiao Xu, Kunlun Huang, Xiaoyun He
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324017408
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author Xiao Han
Bingxin Huangfu
Tongxiao Xu
Kunlun Huang
Xiaoyun He
author_facet Xiao Han
Bingxin Huangfu
Tongxiao Xu
Kunlun Huang
Xiaoyun He
author_sort Xiao Han
collection DOAJ
description Zearalenone (ZEA), produced by Fusarium, is a fungal toxin commonly found in maize, wheat, and other cereals. ZEA has the ability to bind to estrogen receptors of humans and animals and is an environmental endocrine disruptor that may interfere with glucose homeostasis and lipid metabolism. In this study, we first investigated the effects of chronic exposure to low doses of ZEA with a high-fat-diet (HFD) in obese C57BL/6 J mice. In the absence of significant toxicity and without affecting glucose tolerance, 50 and 100 μg/kg b. w. ZEA was found to significantly exacerbate lipid synthesis, accumulation and alter the overall transcriptional profile of the liver in mice synergistically with HFD. Validation in combination with AML-12 cells revealed that ZEA promoted lipid synthesis and increased hepatic lipid droplet accumulation via the HNF1β/PPARγ and SREBP1c-HSD17B13/PLINs signal pathways. Further, by analyzing the changes in the intestinal flora of mice and their relationship with lipid metabolism genes, it was found that ZEA decreased the relative abundance of Lactobacillus and increased the relative abundance of Ileococcus, E. faecalis, and Ricardia. These changes were significantly correlated with the expression of Pparg and Srebf1, etc. ZEA may contribute to the abnormality of lipid metabolism by influencing the intestinal microbiota. This study highlights the synergistic effects of long-term low-dose ZEA and excess lipids, providing a theoretical basis for elucidating the mechanism of chronic toxicity of ZEA and its negative impact on metabolic diseases.
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spelling doaj-art-d3466eb476c243248edcc5c51a09f2252025-01-23T05:26:01ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117664Zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiotaXiao Han0Bingxin Huangfu1Tongxiao Xu2Kunlun Huang3Xiaoyun He4Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety),Ministry of Agriculture and Rural Affairs of the P.R. China, Beijing 100083, China; Corresponding authors at: Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety),Ministry of Agriculture and Rural Affairs of the P.R. China, Beijing 100083, China; Corresponding authors at: Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.Zearalenone (ZEA), produced by Fusarium, is a fungal toxin commonly found in maize, wheat, and other cereals. ZEA has the ability to bind to estrogen receptors of humans and animals and is an environmental endocrine disruptor that may interfere with glucose homeostasis and lipid metabolism. In this study, we first investigated the effects of chronic exposure to low doses of ZEA with a high-fat-diet (HFD) in obese C57BL/6 J mice. In the absence of significant toxicity and without affecting glucose tolerance, 50 and 100 μg/kg b. w. ZEA was found to significantly exacerbate lipid synthesis, accumulation and alter the overall transcriptional profile of the liver in mice synergistically with HFD. Validation in combination with AML-12 cells revealed that ZEA promoted lipid synthesis and increased hepatic lipid droplet accumulation via the HNF1β/PPARγ and SREBP1c-HSD17B13/PLINs signal pathways. Further, by analyzing the changes in the intestinal flora of mice and their relationship with lipid metabolism genes, it was found that ZEA decreased the relative abundance of Lactobacillus and increased the relative abundance of Ileococcus, E. faecalis, and Ricardia. These changes were significantly correlated with the expression of Pparg and Srebf1, etc. ZEA may contribute to the abnormality of lipid metabolism by influencing the intestinal microbiota. This study highlights the synergistic effects of long-term low-dose ZEA and excess lipids, providing a theoretical basis for elucidating the mechanism of chronic toxicity of ZEA and its negative impact on metabolic diseases.http://www.sciencedirect.com/science/article/pii/S0147651324017408ZearalenoneObesityLiverLipid metabolismGut flora
spellingShingle Xiao Han
Bingxin Huangfu
Tongxiao Xu
Kunlun Huang
Xiaoyun He
Zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota
Ecotoxicology and Environmental Safety
Zearalenone
Obesity
Liver
Lipid metabolism
Gut flora
title Zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota
title_full Zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota
title_fullStr Zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota
title_full_unstemmed Zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota
title_short Zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota
title_sort zearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota
topic Zearalenone
Obesity
Liver
Lipid metabolism
Gut flora
url http://www.sciencedirect.com/science/article/pii/S0147651324017408
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AT bingxinhuangfu zearalenoneexacerbateslipidmetabolismdisordersbypromotingliverlipiddropletformationanddisruptinggutmicrobiota
AT tongxiaoxu zearalenoneexacerbateslipidmetabolismdisordersbypromotingliverlipiddropletformationanddisruptinggutmicrobiota
AT kunlunhuang zearalenoneexacerbateslipidmetabolismdisordersbypromotingliverlipiddropletformationanddisruptinggutmicrobiota
AT xiaoyunhe zearalenoneexacerbateslipidmetabolismdisordersbypromotingliverlipiddropletformationanddisruptinggutmicrobiota