Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic
Abstract The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disea...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-04-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202002715 |
| _version_ | 1818672927646679040 |
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| author | Yingyun Gong Yanfeng Xue Xin Li Zhao Zhang Wenjun Zhou Paola Marcolongo Angiolo Benedetti Shengyong Mao Leng Han Guolian Ding Zheng Sun |
| author_facet | Yingyun Gong Yanfeng Xue Xin Li Zhao Zhang Wenjun Zhou Paola Marcolongo Angiolo Benedetti Shengyong Mao Leng Han Guolian Ding Zheng Sun |
| author_sort | Yingyun Gong |
| collection | DOAJ |
| description | Abstract The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disease Registry priority list of hazardous substances. Here, we assess cross‐generational effects of iAs in an exclusive male‐lineage transmission paradigm. The exposure of male mice to 250 ppb iAs causes glucose intolerance and hepatic insulin resistance in F1 females, but not males, without affecting body weight. Hepatic expression of glucose metabolic genes, glucose output, and insulin signaling are disrupted in F1 females. Inhibition of the glucose 6‐phosphatase complex masks the intergenerational effect of iAs, demonstrating a causative role of hepatic glucose production. F2 offspring from grandpaternal iAs exposure show temporary growth retardation at an early age, which diminishes in adults. However, reduced adiposity persists into middle age and is associated with altered gut microbiome and increased brown adipose thermogenesis. In contrast, F3 offspring of the male‐lineage iAs exposure show increased adiposity, especially on a high‐calorie diet. These findings have unveiled sex‐ and generation‐specific heritable effects of iAs on metabolic physiology, which has broad implications in understanding gene‐environment interactions. |
| first_indexed | 2024-12-17T07:47:41Z |
| format | Article |
| id | doaj.art-ada0c5249ca6494a864347dea4e5d5be |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-17T07:47:41Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-ada0c5249ca6494a864347dea4e5d5be2022-12-21T21:57:57ZengWileyAdvanced Science2198-38442021-04-0187n/an/a10.1002/advs.202002715Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic ArsenicYingyun Gong0Yanfeng Xue1Xin Li2Zhao Zhang3Wenjun Zhou4Paola Marcolongo5Angiolo Benedetti6Shengyong Mao7Leng Han8Guolian Ding9Zheng Sun10Department of Endocrinology and Metabolism The First Affiliated Hospital of Nanjing Medical University Nanjing 210029 ChinaDivision of Endocrinology Department of Medicine Baylor College of Medicine Houston TX 77030 USADivision of Endocrinology Department of Medicine Baylor College of Medicine Houston TX 77030 USADepartment of Biochemistry and Molecular Biology McGovern Medical School University of Texas Health Science Center at Houston Houston TX 77030 USADivision of Endocrinology Department of Medicine Baylor College of Medicine Houston TX 77030 USADepartment of Molecular and Developmental Medicine University of Siena Siena 53100 ItalyDepartment of Molecular and Developmental Medicine University of Siena Siena 53100 ItalyNational Center for International Research on Animal Gut Nutrition College of Animal Science and Technology Nanjing Agricultural University Nanjing 210095 ChinaDepartment of Biochemistry and Molecular Biology McGovern Medical School University of Texas Health Science Center at Houston Houston TX 77030 USADivision of Endocrinology Department of Medicine Baylor College of Medicine Houston TX 77030 USADivision of Endocrinology Department of Medicine Baylor College of Medicine Houston TX 77030 USAAbstract The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disease Registry priority list of hazardous substances. Here, we assess cross‐generational effects of iAs in an exclusive male‐lineage transmission paradigm. The exposure of male mice to 250 ppb iAs causes glucose intolerance and hepatic insulin resistance in F1 females, but not males, without affecting body weight. Hepatic expression of glucose metabolic genes, glucose output, and insulin signaling are disrupted in F1 females. Inhibition of the glucose 6‐phosphatase complex masks the intergenerational effect of iAs, demonstrating a causative role of hepatic glucose production. F2 offspring from grandpaternal iAs exposure show temporary growth retardation at an early age, which diminishes in adults. However, reduced adiposity persists into middle age and is associated with altered gut microbiome and increased brown adipose thermogenesis. In contrast, F3 offspring of the male‐lineage iAs exposure show increased adiposity, especially on a high‐calorie diet. These findings have unveiled sex‐ and generation‐specific heritable effects of iAs on metabolic physiology, which has broad implications in understanding gene‐environment interactions.https://doi.org/10.1002/advs.202002715arsenicdiabetesenvironmental healthepigenetic inheritancemetabolismobesity |
| spellingShingle | Yingyun Gong Yanfeng Xue Xin Li Zhao Zhang Wenjun Zhou Paola Marcolongo Angiolo Benedetti Shengyong Mao Leng Han Guolian Ding Zheng Sun Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic Advanced Science arsenic diabetes environmental health epigenetic inheritance metabolism obesity |
| title | Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic |
| title_full | Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic |
| title_fullStr | Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic |
| title_full_unstemmed | Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic |
| title_short | Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic |
| title_sort | inter and transgenerational effects of paternal exposure to inorganic arsenic |
| topic | arsenic diabetes environmental health epigenetic inheritance metabolism obesity |
| url | https://doi.org/10.1002/advs.202002715 |
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