期刊
ENVIRONMENTAL POLLUTION
卷 307, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.envpol.2022.119579
关键词
DEHP; Lipogenesis; Fatty acid composition; SBP-1; SREBP; ER stress
资金
- Ministry of Science and Technology of Taiwan [105-2320-B-002-024-MY3, 108-2320-B-002-014-MY3]
This study investigated the obesogenic effects of chronic DEHP exposure and its mechanisms. The results showed that early-life DEHP exposure led to lipid and triglyceride accumulation, mainly attributed to DEHP itself. The developmental stage and exposure timing influenced DEHP-induced TG accumulation, and chronic exposure had the most significant effect. In addition, chronic DEHP exposure altered fatty acid composition and TG by regulating lipogenic genes.
DEHP is commonly found in the environment, biota, food, and humans, raising significant health concerns. Whether developmental stage and exposure duration modify the obesogenic effects of DEHP is unclear, especially the underlying mechanisms by which chronic exposure to DEHP as well as its metabolites remain largely unknown. This study investigated the obesogenic effects of chronic DEHP exposure, with levels below environmentally-relevant amounts and provide the mechanism in Caenorhabditis elegans. We show that early-life DEHP exposure resulted in an increased lipid and triglyceride (TG) accumulation mainly attributed to DEHP itself, not its metabolite mono-2-ethylhexyl phthalate (MEHP). In addition, developmental stage and exposure timing influence DEHP-induced TG accumulation and chronic DEHP exposure resulted in the most significant effect. Analysis of fatty acid composition shows that chronic DEHP exposure altered fatty acid composition and TG, resulting in an increased co-6/co-3 ratio. The increased TG content by chronic DEHP exposure required lipogenic genes fat-6, fat-7, pod-2, fasn-1, and sbp-1. Moreover, chronic DEHP exposure induced XBP-1-mediated endoplasmic reticulum (ER) stress which might lead to up-regulation of sbp-1. This study suggests the possible involvement of ER stress and SBP-1/SREBP-mediated lipogenesis in chronic DEHP-induced obesogenic effects. Results from this study implies that chronic exposure to DEHP disrupts lipid metabolism, which is likely conserved across species due to evolutionary conservation of molecular mechanisms, raising concerns in ecological and human health.
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