Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice
Endocrine-disrupting chemicals (EDCs), including phthalates, have been implicated in the development of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis. This study investigates the age-dependent effects of butyl benzyl phthalate (BBP) exposure on lipid metabolism in the livers of youn...
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2025-01-01
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| author | Min-Seo Park Seonhwa Hwang Hyun-Bon Kang Minjeong Ha Juyeon Park So-Youn Park Yong-Joo Park Min-Hi Park |
| author_facet | Min-Seo Park Seonhwa Hwang Hyun-Bon Kang Minjeong Ha Juyeon Park So-Youn Park Yong-Joo Park Min-Hi Park |
| author_sort | Min-Seo Park |
| collection | DOAJ |
| description | Endocrine-disrupting chemicals (EDCs), including phthalates, have been implicated in the development of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis. This study investigates the age-dependent effects of butyl benzyl phthalate (BBP) exposure on lipid metabolism in the livers of young and aged mice. Young (2-month-old) and aged (20-month-old) male C57BL/6 mice were exposed to BBP through drinking water at a dose of 169 μg/kg/day for 6 and 4 months, respectively. Young mice exposed to BBP showed fatty liver, with downregulation of key fatty acid oxidation genes (CPT1A, CPT1B, CPT2, and Acox1) and elevated pro-inflammatory cytokines (TNF-α and IL-6). In contrast, aged mice exhibited hepatic fibrosis, with increased collagen deposition and upregulation of genes related to fibrosis (Acta2, MMP2, TGF-ß1, and Col1a2), cirrhosis (CXCR4, SOX9, DCN, and MFAP4), and cancer (Bcl2, CDKN2a, c-Myc, and Fn1). Overall, these findings emphasize the importance of age when evaluating the risks of EDC exposure, such as BBP. Future research should focus on understanding the molecular mechanisms behind these age-related differences and explore Grem1 and SOCS3 as potential therapeutic targets for treating EDC-induced and age-related liver diseases. |
| format | Article |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Cells |
| spelling | doaj-art-a56779aad946426f9404d5f6a14b22412025-01-24T13:26:46ZengMDPI AGCells2073-44092025-01-0114212610.3390/cells14020126Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in MiceMin-Seo Park0Seonhwa Hwang1Hyun-Bon Kang2Minjeong Ha3Juyeon Park4So-Youn Park5Yong-Joo Park6Min-Hi Park7College of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaDepartment of Pharmaceutical Science and Technology, Kyungsung University, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaEndocrine-disrupting chemicals (EDCs), including phthalates, have been implicated in the development of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis. This study investigates the age-dependent effects of butyl benzyl phthalate (BBP) exposure on lipid metabolism in the livers of young and aged mice. Young (2-month-old) and aged (20-month-old) male C57BL/6 mice were exposed to BBP through drinking water at a dose of 169 μg/kg/day for 6 and 4 months, respectively. Young mice exposed to BBP showed fatty liver, with downregulation of key fatty acid oxidation genes (CPT1A, CPT1B, CPT2, and Acox1) and elevated pro-inflammatory cytokines (TNF-α and IL-6). In contrast, aged mice exhibited hepatic fibrosis, with increased collagen deposition and upregulation of genes related to fibrosis (Acta2, MMP2, TGF-ß1, and Col1a2), cirrhosis (CXCR4, SOX9, DCN, and MFAP4), and cancer (Bcl2, CDKN2a, c-Myc, and Fn1). Overall, these findings emphasize the importance of age when evaluating the risks of EDC exposure, such as BBP. Future research should focus on understanding the molecular mechanisms behind these age-related differences and explore Grem1 and SOCS3 as potential therapeutic targets for treating EDC-induced and age-related liver diseases.https://www.mdpi.com/2073-4409/14/2/126endocrine-disrupting chemicals (EDCs)butyl benzyl phthalatenon-alcoholic fatty liver diseasehepatic fibrosisaging |
| spellingShingle | Min-Seo Park Seonhwa Hwang Hyun-Bon Kang Minjeong Ha Juyeon Park So-Youn Park Yong-Joo Park Min-Hi Park Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice Cells endocrine-disrupting chemicals (EDCs) butyl benzyl phthalate non-alcoholic fatty liver disease hepatic fibrosis aging |
| title | Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice |
| title_full | Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice |
| title_fullStr | Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice |
| title_full_unstemmed | Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice |
| title_short | Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice |
| title_sort | age dependent effects of butyl benzyl phthalate exposure on lipid metabolism and hepatic fibrosis in mice |
| topic | endocrine-disrupting chemicals (EDCs) butyl benzyl phthalate non-alcoholic fatty liver disease hepatic fibrosis aging |
| url | https://www.mdpi.com/2073-4409/14/2/126 |
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