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Lipin1 is a key factor for the maturation and maintenance of adipocytes in the regulatory network with CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma 2.

Authors
 Yoo-Kyung Koh  ;  Min-Young Lee  ;  Jae-Woo Kim  ;  Minji Kim  ;  Jong-Seok Moon  ;  Yoo-Jung Lee  ;  Yong-Ho Ahn  ;  Kyung-Sup Kim 
Citation
 Journal of Biological Chemistry, Vol.283(50) : 34896-34906, 2008 
Journal Title
 Journal of Biological Chemistry 
ISSN
 0021-9258 
Issue Date
2008
MeSH
3T3-L1 Cells ; Adipocytes/metabolism ; Animals ; CCAAT-Enhancer-Binding Protein-alpha/metabolism* ; Cell Differentiation ; DNA-Binding Proteins/metabolism ; Liver X Receptors ; Mice ; Models, Biological ; NIH 3T3 Cells ; Nuclear Proteins/chemistry* ; Oligonucleotides/chemistry ; Orphan Nuclear Receptors ; PPAR gamma/metabolism* ; Phosphatidate Phosphatase ; Plasmids/metabolism ; RNA, Small Interfering/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Sterol Regulatory Element Binding Protein 1/metabolism
Keywords
3T3-L1 Cells ; Adipocytes/metabolism ; Animals ; CCAAT-Enhancer-Binding Protein-alpha/metabolism* ; Cell Differentiation ; DNA-Binding Proteins/metabolism ; Liver X Receptors ; Mice ; Models, Biological ; NIH 3T3 Cells ; Nuclear Proteins/chemistry* ; Oligonucleotides/chemistry ; Orphan Nuclear Receptors ; PPAR gamma/metabolism* ; Phosphatidate Phosphatase ; Plasmids/metabolism ; RNA, Small Interfering/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Sterol Regulatory Element Binding Protein 1/metabolism
Abstract
Lipin1 expression was induced at a late stage of differentiation of 3T3-L1 preadipocytes and maintained at high levels in mature adipocytes. Knockdown of expression of lipin1 by small interfering RNA in 3T3-L1 preadipocytes almost completely inhibited differentiation into adipocytes, whereas overexpression of lipin1 accelerated adipocyte differentiation, demonstrating that lipin1 is required for adipocyte differentiation. In mature adipocytes, transfection of lipin1-small interfering RNA decreased the expression of adipocyte functional genes, indicating the involvement of lipin1 in the maintenance of adipocyte function. Lipin1 increases the transcription-activating function of peroxisome proliferator-activated receptor gamma(2) (PPAR gamma(2)) via direct physical interaction, whereas lipin1 did not affect the function of other adipocyte-related transcription factors such as C/EBP alpha, liver X-activated receptor alpha, or sterol regulatory element binding protein 1c. In mature adipocytes, lipin1 was specifically recruited to the PPAR gamma-response elements of the phosphoenolpyruvate carboxykinase gene, an adipocyte-specific gene. C/EBP alpha up-regulates lipin1 transcription by directly binding to the lipin1 promoter. Based on the existence of a positive feedback loop between C/EBP alpha and PPAR gamma(2), we propose that lipin1 functions as an amplifier of the network between these factors, resulting in the maintenance of high levels of the specific gene expression that are required for adipogenesis and mature adipocyte functions.
Files in This Item:
T200801626.pdf Download
DOI
10.1074/jbc.M804007200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Lee, Min Young(이민영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107962
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