Triflumizole is an obesogen in mice that acts through peroxisome proliferator activated receptor gamma (PPARγ).
Triflumizole is an obesogen in mice that acts through peroxisome proliferator activated receptor gamma (PPARγ).
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DOI：
10.1289/ehp.1205383
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发表时间：
2012-12
影响因子：
10.4
通讯作者：
Blumberg B
中科院分区：
文献类型：
--
作者：
Li X;Pham HT;Janesick AS;Blumberg B
背景：三氟咪唑(Triflumizole，TFZ)是一种咪唑类杀菌剂，用于多种食品和观赏作物。TFZ被认为没有特别的毒性或致癌作用，但人们对其对发育的影响知之甚少。Tfz在ToxCast中被鉴定为一种过氧化物酶体增殖物激活受体γ(PPARγ)激活剂。因为PPARγ是脂肪生成的主要调节因子，我们假设TFZ会激活PPARγ，从而在体内诱导脂肪生成和体重增加。目的：在体外和体内实验中，我们试图测试TFZ激活PPARγ和促进脂肪生成的能力。方法：用瞬时转染法检测TFZ激活PPARγ的能力，并用3T3-L1前脂肪细胞和人多能间充质干细胞在体外培养条件下研究TFZ的成脂能力。我们用三种剂量的TFZ治疗怀孕的小鼠，并评估了对产前暴露的后代的体重、脂肪库重和MSC编程的影响。讨论：TFZ诱导骨髓间充质干细胞和小鼠3T3-L1前脂肪细胞成脂。产前暴露于TFZ水平大约是报告的未观察到不良反应水平的400倍，增加了脂肪库重。所有剂量的TFZ在促进MSCs成脂基因表达的同时抑制成骨基因的表达。结论：TFZ在低纳摩尔浓度下通过PPARγ依赖机制诱导MSCs和前脂肪细胞成脂分化。产前接触TFZ会增加脂肪储存重量，并将MSC的命运转向脂肪细胞谱系；因此，我们得出结论，TFZ在体内是一种致肥者。
Background: 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 PPARγ is a master regulator of adipogenesis, we hypothesized that TFZ would activate PPARγ, thereby inducing adipogenesis and weight gain in vivo. Objectives: We sought to test the ability of TFZ to activate PPARγ and promote adipogenesis in vitro and in vivo. Methods: 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 prenatally exposed offspring. Discussion: TFZ induced adipogenesis 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. Conclusions: TFZ acts through a PPARγ-dependent mechanism to induce adipogenic differentiation 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.
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影响因子：
120.7
作者：
Flegal, Katherine M.;Carroll, Margaret D.;Curtin, Lester R.
通讯作者：
Curtin, Lester R.
影响因子：
56.9
作者：
Hill, JO;Peters, JC
通讯作者：
Peters, JC
影响因子：
--
作者：
La Merrill, Michele;Birnbaum, Linda S.
通讯作者：
Birnbaum, Linda S.
DOI：
10.1007/978-1-4419-7034-3_17
发表时间：
2011-01-01
期刊：
OBESITY BEFORE BIRTH: MATERNAL AND PRENATAL INFLUENCES ON THE OFFSPRING
影响因子：
--
作者：
Heindel, Jerrold J.
通讯作者：
Heindel, Jerrold J.
DOI：
10.1097/mco.0b013e3283034990
发表时间：
2008-07-01
影响因子：
3.1
作者：
Herbert, Alan
通讯作者：
Herbert, Alan