title: PPARγ agonists induce adipocyte differentiation by modulating the expression of Lipin-1, which acts as a PPARγ phosphatase.
abstract: PPARγ agonists induced obesity in animal models as a side effect. Microarray experiments reveal that PPARγ agonist upregulates the expression of lipin-1 and this upregulation is correlated with the activity of the agonists. Lipin-1 induced by PPARγ agonists decreased the levels of PPARγ and ERK1/2 phosphorylation through direct interaction with these proteins in 3T3-L1 cells. In PPARγ agonist-treated 3T3-L1 preadipocytes, the knockdown of lipin-1 expression by small interfering RNA inhibited the adipogenesis that was induced by PPARγ agonists. In contrast, PPARγ2 expression was increased, and lipid droplets were accumulated in lipin-1-overexpressing 3T3-L1 adipocytes. Rosiglitazone (RGZ), a strong PPARγ agonist, synergistically promoted PPARγ dephosphorylation and adipogenesis in lipin-1-overexpressing 3T3-L1 preadipocytes. Therefore, lipin-1 has dual functions as a transcriptional cofactor and phosphatidate phosphatase (PAP) in the differentiation of preadipocyte cells induced by strong PPARγ agonists. In addition, the adipogenesis of 3T3-L1 cells was markedly upregulated by diacylglycerol (DAG), which was produced by lipin-1. Therefore, lipin-1 induction by PPARγ agonists might be an important factor in understanding the biological mechanism of the agonists' adverse effects, and this information may be valuable in the development of type-2 diabetes mellitus (T2DM) therapeutics with reduced adverse effects and greater tolerability.
authors: Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
authors: Jina
authors: J
authors: Kim
authors: Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea; University of Science and Technology in Korea, Republic of Korea.
authors: Yu-Jin
authors: YJ
authors: Lee
authors: Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
authors: Jung Min
authors: JM
authors: Kim
authors: Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
authors: So Young
authors: SY
authors: Lee
authors: Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.
authors: Myung-Ae
authors: MA
authors: Bae
authors: Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.
authors: Jin Hee
authors: JH
authors: Ahn
authors: Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea; University of Science and Technology in Korea, Republic of Korea.
authors: Dong Cho
authors: DC
authors: Han
authors: Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea; University of Science and Technology in Korea, Republic of Korea. Electronic address: kwonbm@kribb.re.kr.
authors: Byoung-Mog
authors: BM
authors: Kwon
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D004075:Diglycerides / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D047495:PPAR gamma / Q000819:agonists*; D010711:Phosphatidate Phosphatase / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D004075:Diglycerides; D009687:Nuclear Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase
keywords: Adipocytes; Lipin-1; Obesity; PPARγ; PPARγ agonists; Phosphatase