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Tributyltin triggers lipogenesis in macrophages via modifying PPARγ pathway.
Jie, Jiapeng; Ling, Ling; Yi, Yuguo; Tao, Liang; Liao, Xin; Gao, Pingshi; Xu, Qian; Zhang, Weigao; Chen, Yuxin; Zhang, Jianfa; Weng, Dan.
Afiliação
  • Jie J; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
  • Ling L; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
  • Yi Y; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
  • Tao L; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
  • Liao X; Guangxi Mangrove Research Center, Guangxi Key Lab of Mangrove Conservation and Utilization, Beihai, 536000, China.
  • Gao P; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
  • Xu Q; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
  • Zhang W; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
  • Chen Y; Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, China.
  • Zhang J; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
  • Weng D; School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing, 210094, China. Electronic address: danweng@njust.edu.cn.
Environ Pollut ; 271: 116331, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33383419
ABSTRACT
Tributyltin (TBT), a bioaccumulative and persistent environmental pollutant, has been proposed as a metabolism disruptor and obesogen through targeting peroxisome proliferator-activated receptor gamma (PPARγ) receptor pathway. However, it remains unknown whether this biological effect occurs in macrophage, a cell type which cooperates closely with hepatocytes and adipocytes to regulate lipid metabolism. This study for the first time investigated the effect of TBT on PPARγ pathway in macrophages. Our results indicated that nanomolar levels of TBT was able to strongly activate PPARγ in human macrophages. TBT treatment also markedly increased the intracellular lipid accumulation, and enhanced the expression of lipid metabolism-related genes in macrophages, while these effects were all significantly down-regulated in PPARγ-deficient macrophages, confirming the involvement of PPARγ in TBT-induced lipogenesis. Next, a mouse model that C57BL/6 mice were orally exposed to TBT with the doses (250 and 500 µg/kg body weight) lower than NOAEL (no observed adverse effect level) was used to further investigate the in vivo mechanisms. And the in vivo results were consistent with cellular assays, confirming the induction of PPARγ and the increased expression of lipogenesis-regulating and lipid metabolism-related genes by TBT in vivo. In conclusion, this study not only provided the first evidence that TBT stimulated lipogenesis, activated PPARγ and related genes in human macrophages, but also provided insight into the mechanism of TBT-induced metabolism disturbance and obesity through targeting PPARγ via both in vitro cellular assays and in vivo animal models.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: PPAR gama / Lipogênese Limite: Animais Idioma: Inglês Revista: Environ Pollut Assunto da revista: Saúde Ambiental Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: China

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: PPAR gama / Lipogênese Limite: Animais Idioma: Inglês Revista: Environ Pollut Assunto da revista: Saúde Ambiental Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: China