Lipin1 is a key factor for the maturation and maintenance of adipocytes in the regulatory network with C/EBPα and PPARγ2

Abstract

[한글]

[영문]Lipin1 expression was induced at a late stage of differentiation of 3T3-L1 preadipocytes and maintained at high level in mature adipocytes. Knockdown of expression of lipin1 by small interfering RNA (siRNA) 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-siRNA 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 PPARγ2 via direct physical interaction, whereas lipin1 did not affect the function of other adipocyte-related transcription factors, such as C/EBPα, LXRα or SREBP-1c. In mature adipocytes, lipin1 was specifically recruited to the PPREs of the PEPCK gene, an adipocyte-specific gene. C/EBPα up-regulates lipin1 transcription by directly binding to the lipin1 promoter. Based on the existence of a positive feedback loop between C/EBPα and PPARγ2, 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 is required for adipogenesis and mature adipocyte functions.