Metabolic Phenotype of Wild-Type and As3mt -Knockout C57BL/6J Mice Exposed to Inorganic Arsenic: The Role of Dietary Fat and Folate Intake
| Autor: | Chongben Zhang, Sergey A. Krupenko, Christelle Douillet, Madelyn C. Huang, Rowan Beck, Ahmad Tejan-Sie, Ellen N. Dover, Miroslav Stýblo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Inorganic arsenic Health Toxicology and Mutagenesis 010501 environmental sciences Biology 01 natural sciences Arsenic Mice 03 medical and health sciences Folic Acid Insulin resistance Diabetes mellitus Internal medicine medicine Animals Folate intake 0105 earth and related environmental sciences Mice Knockout 2. Zero hunger Arsenic toxicity Research Public Health Environmental and Occupational Health Wild type Methyltransferases Metabolism medicine.disease Dietary Fats Phenotype Mice Inbred C57BL 030104 developmental biology Endocrinology Insulin Resistance |
| Zdroj: | Environmental Health Perspectives |
| ISSN: | 1552-9924 0091-6765 |
| Popis: | Background: Inorganic arsenic (iAs) is a diabetogen. Interindividual differences in iAs metabolism have been linked to susceptibility to diabetes in iAs-exposed populations. Dietary folate intake has been shown to influence iAs metabolism, but to our knowledge its role in iAs-associated diabetes has not been studied. Objective: The goal of this study was to assess how folate intake, combined with low-fat (LFD) and high-fat diets (HFD), affects the metabolism and diabetogenic effects of iAs in wild-type (WT) mice and in As3mt-knockout (KO) mice that have limited capacity for iAs detoxification. Methods: Male and female WT and KO mice were exposed to 0 or 100 ppb iAs in drinking water. Mice were fed the LFD containing 0.2 mg/kg or 10 mg/kg folate for 24 weeks, followed by the HFD with the same folate levels for 13 weeks. Metabolic phenotype and iAs metabolism were examined before and after switching to the HFD. Results: iAs exposure had little effect on the phenotype of mice fed LFD regardless of folate intake. High folate intake stimulated iAs metabolism, but only in WT females. KO mice accumulated more fat than WT mice and were insulin resistant, with males more insulin resistant than females despite similar %fat mass. Feeding the HFD increased adiposity and insulin resistance in all mice. However, iAs-exposed male and female WT mice with low folate intake were more insulin resistant than unexposed controls. High folate intake alleviated insulin resistance in both sexes, but stimulated iAs metabolism only in female mice. Conclusions: Exposure to 100 ppb iAs in drinking water resulted in insulin resistance in WT mice only when combined with a HFD and low folate intake. The protective effect of high folate intake may be independent of iAs metabolism, at least in male mice. KO mice were more prone to developing insulin resistance, possibly due to the accumulation of iAs in tissues. https://doi.org/10.1289/EHP3951 |
| Databáze: | OpenAIRE |
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