文章基本信息

标题：Triflumizole Is an Obesogen in Mice that Acts through Peroxisome Proliferator Activated Receptor Gamma (PPARγ)
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作者：Xia Li ; Hang T. Pham ; Amanda S. Janesick 等
期刊名称：Environmental Health Perspectives
印刷版ISSN：0091-6765
电子版ISSN：1552-9924
出版年度：2012
卷号：120
期号：12
页码：1720-1726
DOI：10.1289/ehp.1205383
出版社：OCR Subscription Services Inc
摘要：a c k g r o u n d: Triflumizole (TFZ) is an imidazole fungicide used on many food and ornamental crops. TFZ is not thought to be particularly toxic or carcinogenic, but little is known about its effect on development. TFZ is identified as a peroxisome proliferator activated receptor gamma (PPARγ) activator in ToxCast. Because PPARγis a master regulator of adipo genesis, we hypothesized that TFZ would activate PPARγ, thereby inducing adipo genesis and weight gain in vivo.oB j e c t i ve s: We sought to test the ability of TFZ to activate PPARγand promote adipo genesis in vitro and in vivo.Me t h o d s: We used transient transfection to test the ability of TFZ to activate PPARγ, and we used 3T3-L1 preadipocytes and human multipotent mesenchymal stromal stem cells (MSCs) to study the adipogenic capacity of TFZ in culture. We treated pregnant mice with three doses of TFZ and evaluated the effects on body weight, adipose depot weight, and MSC programming in the pre-natally exposed offspring.di sc us si o n: TFZ induced adipo genesis in MSCs and in mouse 3T3-L1 preadipocytes. Prenatal exposure to levels of TFZ at approximately 400-fold below the reported no observed adverse effect level increased adipose depot weight. All doses of TFZ tested increased adipogenic gene expression in MSCs while inhibiting expression of osteogenic genes.co n c l u s i o n s: TFZ acts through a PPARγ-dependent mechanism to induce adipogenic differentia-tion in MSCs and preadipocytes at low nanomolar concentrations. Prenatal TFZ exposure increases adipose depot weight and diverts MSC fate toward the adipocyte lineage; therefore, we conclude that TFZ is an obesogen in vivo
关键词：3T3-L1 cells; adipo ;genesis; endocrine disruption; MSCs; obesogen; PPAR;γ; triflumizole