Chronic BPAF exposure differentially enhances fat deposition in mice fed normal or high-fat diets via lipid metabolism dysregulation

BackgroundBisphenol AF (BPAF), an alternative to Bisphenol A (BPA), is increasingly utilized in various industrial applications, yet its toxicological profile remains incompletely understood. This study aims to investigate the impact of BPAF exposure on obesity and lipid metabolism in male mice subj...

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Main Authors: Ziquan Lv, Xinyue Xu, Zhi Tang, Yin Liang, Changfeng Peng, Yuxuan Wu, Dan Sang, Guixuan Jia, Xiaoxiao Hu, Ying Chen, Guangnan Liu, Dan Wang, Suli Huang, Yajie Guo
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1571076/full
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author Ziquan Lv
Ziquan Lv
Xinyue Xu
Xinyue Xu
Zhi Tang
Yin Liang
Changfeng Peng
Yuxuan Wu
Yuxuan Wu
Dan Sang
Guixuan Jia
Xiaoxiao Hu
Ying Chen
Guangnan Liu
Dan Wang
Suli Huang
Yajie Guo
author_facet Ziquan Lv
Ziquan Lv
Xinyue Xu
Xinyue Xu
Zhi Tang
Yin Liang
Changfeng Peng
Yuxuan Wu
Yuxuan Wu
Dan Sang
Guixuan Jia
Xiaoxiao Hu
Ying Chen
Guangnan Liu
Dan Wang
Suli Huang
Yajie Guo
author_sort Ziquan Lv
collection DOAJ
description BackgroundBisphenol AF (BPAF), an alternative to Bisphenol A (BPA), is increasingly utilized in various industrial applications, yet its toxicological profile remains incompletely understood. This study aims to investigate the impact of BPAF exposure on obesity and lipid metabolism in male mice subjected to either a normal chow diet (ND) or a high-fat diet (HFD).MethodsMice were exposed to BPAF at a concentration of 100 μg/kg every other day for five months under different dietary conditions, and body weight, rectal temperature, and food intake were monitored regularly. After the mice were sacrificed, the hepatic lipid metabolism was analyzed by measuring serum, hepatic lipids and performing hepatic metabolomics; energy metabolism was elucidated by assessing thermogenic pathways in brown adipose tissue (BAT) and factors affecting ingestion in the hypothalamus; the development and pathways of obesity were indicated by exploring lipogenesis and lipolysis pathways and fat accumulation in white adipose tissue (WAT).ResultsHistomorphometric analyses indicated that BPAF exposure induced drived fat deposition in white adipose tissue through adipocyte hypertrophy-mediated pathways in eWAT of ND and HFD mice, accompanied by weight gain in HFD mice. Energy metabolism analysis showed that BPAF exposure decreased resting body temperature and reduced thermogenic factor expression in BAT of ND and HFD mice, which may affect energy expenditure. Hepatic metabolomics analysis suggested that BPAF exposure interfered with hepatic lipid metabolism in ND and HFD mice, with elevated levels of hepatic triglycerides, total cholesterol, and free fatty acids in HFD mice. Transcript analysis revealed altered expression levels of genes regulating lipid metabolism in white adipose tissue of ND and HFD mice, with a down-regulation observed in p-HSL protein expression, indicative of a potential inhibition effects of BPAF on lipolysis signaling pathway.ConclusionChronic BPAF exposure differentially exacerbates fat deposition in mice fed normal or high-fat diets via affecting lipid metabolism. Given the widespread prevalence of obesity and the pervasive environmental presence of BPAF, our findings provide valuable insights into the metabolic toxicity of BPAF, thereby raise further concern on the safe utilization and precision prevention of this unique chemical.
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spelling doaj-art-d9983b3da2d94228ad23d686276927202025-08-20T03:49:42ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-05-011610.3389/fendo.2025.15710761571076Chronic BPAF exposure differentially enhances fat deposition in mice fed normal or high-fat diets via lipid metabolism dysregulationZiquan Lv0Ziquan Lv1Xinyue Xu2Xinyue Xu3Zhi Tang4Yin Liang5Changfeng Peng6Yuxuan Wu7Yuxuan Wu8Dan Sang9Guixuan Jia10Xiaoxiao Hu11Ying Chen12Guangnan Liu13Dan Wang14Suli Huang15Yajie Guo16School of Public Health, University of South China, Hengyang, ChinaDivision of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaSchool of Public Health, University of South China, Hengyang, ChinaDivision of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaDepartment of Environmental and Occupational Health, School of Public Health, Guangdong Medical University, Dongguan, ChinaDepartment of Emergency, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, ChinaDivision of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaSchool of Public Health, University of South China, Hengyang, ChinaDivision of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaDepartment of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, ChinaDepartment of Emergency, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, ChinaDivision of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaDivision of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaDivision of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaDivision of Conservation and Application of Biological Resources, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, ChinaDepartment of Emergency, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, ChinaBackgroundBisphenol AF (BPAF), an alternative to Bisphenol A (BPA), is increasingly utilized in various industrial applications, yet its toxicological profile remains incompletely understood. This study aims to investigate the impact of BPAF exposure on obesity and lipid metabolism in male mice subjected to either a normal chow diet (ND) or a high-fat diet (HFD).MethodsMice were exposed to BPAF at a concentration of 100 μg/kg every other day for five months under different dietary conditions, and body weight, rectal temperature, and food intake were monitored regularly. After the mice were sacrificed, the hepatic lipid metabolism was analyzed by measuring serum, hepatic lipids and performing hepatic metabolomics; energy metabolism was elucidated by assessing thermogenic pathways in brown adipose tissue (BAT) and factors affecting ingestion in the hypothalamus; the development and pathways of obesity were indicated by exploring lipogenesis and lipolysis pathways and fat accumulation in white adipose tissue (WAT).ResultsHistomorphometric analyses indicated that BPAF exposure induced drived fat deposition in white adipose tissue through adipocyte hypertrophy-mediated pathways in eWAT of ND and HFD mice, accompanied by weight gain in HFD mice. Energy metabolism analysis showed that BPAF exposure decreased resting body temperature and reduced thermogenic factor expression in BAT of ND and HFD mice, which may affect energy expenditure. Hepatic metabolomics analysis suggested that BPAF exposure interfered with hepatic lipid metabolism in ND and HFD mice, with elevated levels of hepatic triglycerides, total cholesterol, and free fatty acids in HFD mice. Transcript analysis revealed altered expression levels of genes regulating lipid metabolism in white adipose tissue of ND and HFD mice, with a down-regulation observed in p-HSL protein expression, indicative of a potential inhibition effects of BPAF on lipolysis signaling pathway.ConclusionChronic BPAF exposure differentially exacerbates fat deposition in mice fed normal or high-fat diets via affecting lipid metabolism. Given the widespread prevalence of obesity and the pervasive environmental presence of BPAF, our findings provide valuable insights into the metabolic toxicity of BPAF, thereby raise further concern on the safe utilization and precision prevention of this unique chemical.https://www.frontiersin.org/articles/10.3389/fendo.2025.1571076/fullBPAFhigh-fat dietfat accumulationlipid metabolismobesity
spellingShingle Ziquan Lv
Ziquan Lv
Xinyue Xu
Xinyue Xu
Zhi Tang
Yin Liang
Changfeng Peng
Yuxuan Wu
Yuxuan Wu
Dan Sang
Guixuan Jia
Xiaoxiao Hu
Ying Chen
Guangnan Liu
Dan Wang
Suli Huang
Yajie Guo
Chronic BPAF exposure differentially enhances fat deposition in mice fed normal or high-fat diets via lipid metabolism dysregulation
Frontiers in Endocrinology
BPAF
high-fat diet
fat accumulation
lipid metabolism
obesity
title Chronic BPAF exposure differentially enhances fat deposition in mice fed normal or high-fat diets via lipid metabolism dysregulation
title_full Chronic BPAF exposure differentially enhances fat deposition in mice fed normal or high-fat diets via lipid metabolism dysregulation
title_fullStr Chronic BPAF exposure differentially enhances fat deposition in mice fed normal or high-fat diets via lipid metabolism dysregulation
title_full_unstemmed Chronic BPAF exposure differentially enhances fat deposition in mice fed normal or high-fat diets via lipid metabolism dysregulation
title_short Chronic BPAF exposure differentially enhances fat deposition in mice fed normal or high-fat diets via lipid metabolism dysregulation
title_sort chronic bpaf exposure differentially enhances fat deposition in mice fed normal or high fat diets via lipid metabolism dysregulation
topic BPAF
high-fat diet
fat accumulation
lipid metabolism
obesity
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1571076/full
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