PPARgamma agonists induce adipocyte differentiation by modulating the expression of Lipin-1, which acts as a PPARgamma phosphatase = PPARgamma agonists와 비만과의 관련성

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Title
PPARgamma agonists induce adipocyte differentiation by modulating the expression of Lipin-1, which acts as a PPARgamma phosphatase = PPARgamma agonists와 비만과의 관련성
Author(s)
Jina Kim; Yu Jin Lee; Jung Min Kim; So Young Lee; M A Bae; J H Ahn; Dong Cho Han; Byoung-Mog Kwon
Bibliographic Citation
International Journal of Biochemistry & Cell Biology, vol. 81, no. 1, pp. 57-66
Publication Year
2016
Abstract
PPAR agonists induced obesity in animal models as a side effect. Microarray experiments reveal thatPPAR agonist upregulates the expression of lipin-1 and this upregulation is correlated with the activityof the agonists. Lipin-1 induced by PPAR agonists decreased the levels of PPAR and ERK1/2 phospho-rylation through direct interaction with these proteins in 3T3-L1 cells. In PPAR agonist-treated 3T3-L1preadipocytes, the knockdown of lipin-1 expression by small interfering RNA inhibited the adipogenesisthat was induced by PPAR agonists. In contrast, PPAR 2 expression was increased, and lipid dropletswere accumulated in lipin-1-overexpressing 3T3-L1 adipocytes. Rosiglitazone (RGZ), a strong PPAR agonist, synergistically promoted PPAR dephosphorylation and adipogenesis in lipin-1-overexpressing3T3-L1 preadipocytes. Therefore, lipin-1 has dual functions as a transcriptional cofactor and phosphati-date phosphatase (PAP) in the differentiation of preadipocyte cells induced by strong PPAR agonists.In addition, the adipogenesis of 3T3-L1 cells was markedly upregulated by diacylglycerol (DAG), whichwas produced by lipin-1. Therefore, lipin-1 induction by PPAR agonists might be an important factorin understanding the biological mechanism of the agonists’ adverse effects, and this information maybe valuable in the development of type-2 diabetes mellitus (T2DM) therapeutics with reduced adverseeffects and greater tolerability.
Keyword
Lipin-1PPARAdipocytesPPAR agonistsPhosphataseObesity
ISSN
1357-2725
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.biocel.2016.10.018
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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