Exposure to triphenyl phosphate during pregnancy: The role of gut-bile acids-liver axis on lipid metabolism in male offspring
The widespread use of Triphenyl phosphate (TPhP) as a substitute flame retardant in various commercial products has raised global concerns for its health risks. Previously, we found that gestational and lactational TPhP exposure disturbed lipid metabolism and gut microbiota in offspring sex-dependen...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324016300 |
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| author | Juntong Lin Fuhui Yan Longhui Liu Ganzhong Liao Yilei Xu Qian Liu Miaoliang Wu Honghui Guo Bai Zhi Lianxian Guo Xiaoshan Liu |
| author_facet | Juntong Lin Fuhui Yan Longhui Liu Ganzhong Liao Yilei Xu Qian Liu Miaoliang Wu Honghui Guo Bai Zhi Lianxian Guo Xiaoshan Liu |
| author_sort | Juntong Lin |
| collection | DOAJ |
| description | The widespread use of Triphenyl phosphate (TPhP) as a substitute flame retardant in various commercial products has raised global concerns for its health risks. Previously, we found that gestational and lactational TPhP exposure disturbed lipid metabolism and gut microbiota in offspring sex-dependently. In this study, we further explored the prenatal TPhP exposure on lipid metabolism in male offspring, and the role of gut-bile acids-liver axis in it. The results showed that gestational TPhP exposure would induce hyperlipidemia in male offspring, it dose-dependently increased the weight of body and liver, levels of serum lipid, and enlarged lipid droplets in white adipose tissue. The expression of lipid metabolism-related genes was significantly changed in the liver and adipose tissue. The gut microbiome of male offspring was also altered, with different profiles between the low and high dose treatment group. Target bile acids (BAs) metabolites analysis revealed a significant increased levels of primary BAs cholic acid (CA), but decreased levels of chenodeoxycholic acid (CDCA), and decreased levels of the secondary BAs deoxycholic acid (DCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and lithocholic acid (LCA) in TPhP treatment group. Measurements of gene expression along the gut-BAs-liver axis showed that the TPhP treatment group had an increase in cholesterol-7alpha-hydroxylase (CYP7A1) and a decrease in apical sodium-dependent bile acid transporter (ASBT), with only the low-dose group exhibiting an increase in carbohydrate response element binding protein (ChREBP). Correlation and mediation analysis highlighted associations of Burkholderiaceae in low-dose treatment group and Erysipelotrichaceae in high dose group with lipid metabolism and BAs metabolites. No consistent correlations were observed in two treatment group. Additionally, Mantel tests did not reveal a consistent correlation between the microbiome network community and lipid metabolism or the gut-bile acids-liver axis. Overall, our findings indicate that gestational TPhP exposure induces hyperlipidemia in male offspring, and while the gut-BAs-liver axis plays a role, other mechanisms warrant further investigation. |
| format | Article |
| id | doaj-art-46de5a89919444daaf425e36f7596c4d |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-46de5a89919444daaf425e36f7596c4d2025-02-12T05:29:42ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117554Exposure to triphenyl phosphate during pregnancy: The role of gut-bile acids-liver axis on lipid metabolism in male offspringJuntong Lin0Fuhui Yan1Longhui Liu2Ganzhong Liao3Yilei Xu4Qian Liu5Miaoliang Wu6Honghui Guo7Bai Zhi8Lianxian Guo9Xiaoshan Liu10School of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, China; Shunde Women and Children’s Hospital, Guangdong Medical University, Foshan, Guangdong 528000, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, ChinaSchool of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, China; Corresponding authors.School of Public Health, The first Dongguan affiliated hospital, Guangdong Medical University, Dongguan, Guangdong 523808, China; Corresponding authors.The widespread use of Triphenyl phosphate (TPhP) as a substitute flame retardant in various commercial products has raised global concerns for its health risks. Previously, we found that gestational and lactational TPhP exposure disturbed lipid metabolism and gut microbiota in offspring sex-dependently. In this study, we further explored the prenatal TPhP exposure on lipid metabolism in male offspring, and the role of gut-bile acids-liver axis in it. The results showed that gestational TPhP exposure would induce hyperlipidemia in male offspring, it dose-dependently increased the weight of body and liver, levels of serum lipid, and enlarged lipid droplets in white adipose tissue. The expression of lipid metabolism-related genes was significantly changed in the liver and adipose tissue. The gut microbiome of male offspring was also altered, with different profiles between the low and high dose treatment group. Target bile acids (BAs) metabolites analysis revealed a significant increased levels of primary BAs cholic acid (CA), but decreased levels of chenodeoxycholic acid (CDCA), and decreased levels of the secondary BAs deoxycholic acid (DCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and lithocholic acid (LCA) in TPhP treatment group. Measurements of gene expression along the gut-BAs-liver axis showed that the TPhP treatment group had an increase in cholesterol-7alpha-hydroxylase (CYP7A1) and a decrease in apical sodium-dependent bile acid transporter (ASBT), with only the low-dose group exhibiting an increase in carbohydrate response element binding protein (ChREBP). Correlation and mediation analysis highlighted associations of Burkholderiaceae in low-dose treatment group and Erysipelotrichaceae in high dose group with lipid metabolism and BAs metabolites. No consistent correlations were observed in two treatment group. Additionally, Mantel tests did not reveal a consistent correlation between the microbiome network community and lipid metabolism or the gut-bile acids-liver axis. Overall, our findings indicate that gestational TPhP exposure induces hyperlipidemia in male offspring, and while the gut-BAs-liver axis plays a role, other mechanisms warrant further investigation.http://www.sciencedirect.com/science/article/pii/S0147651324016300Flame retardantsGut microbiotaGut-bile acids-liver axisLipid metabolism |
| spellingShingle | Juntong Lin Fuhui Yan Longhui Liu Ganzhong Liao Yilei Xu Qian Liu Miaoliang Wu Honghui Guo Bai Zhi Lianxian Guo Xiaoshan Liu Exposure to triphenyl phosphate during pregnancy: The role of gut-bile acids-liver axis on lipid metabolism in male offspring Ecotoxicology and Environmental Safety Flame retardants Gut microbiota Gut-bile acids-liver axis Lipid metabolism |
| title | Exposure to triphenyl phosphate during pregnancy: The role of gut-bile acids-liver axis on lipid metabolism in male offspring |
| title_full | Exposure to triphenyl phosphate during pregnancy: The role of gut-bile acids-liver axis on lipid metabolism in male offspring |
| title_fullStr | Exposure to triphenyl phosphate during pregnancy: The role of gut-bile acids-liver axis on lipid metabolism in male offspring |
| title_full_unstemmed | Exposure to triphenyl phosphate during pregnancy: The role of gut-bile acids-liver axis on lipid metabolism in male offspring |
| title_short | Exposure to triphenyl phosphate during pregnancy: The role of gut-bile acids-liver axis on lipid metabolism in male offspring |
| title_sort | exposure to triphenyl phosphate during pregnancy the role of gut bile acids liver axis on lipid metabolism in male offspring |
| topic | Flame retardants Gut microbiota Gut-bile acids-liver axis Lipid metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324016300 |
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