Lipin1 Is a Key Factor for the Maturation and Maintenance of Adipocytes in the Regulatory Network with CCAAT/Enhancer-binding Protein α and Peroxisome Proliferator-activated Receptor γ2
Copyright policy )Lipin1 Is a Key Factor for the Maturation and Maintenance of Adipocytes in the Regulatory Network with CCAAT/Enhancer-binding Protein α and Peroxisome Proliferator-activated Receptor γ2
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.
- Yonsei University Korea (Republic of)
- Yonsei University Medical Library Korea (Republic of)
- Yonsei University Health System Korea (Republic of)
Small Interfering/metabolism, Oligonucleotides, Phosphatidate Phosphatase, 610, Receptors, Cytoplasmic and Nuclear, Cytoplasmic and Nuclear/metabolism, Models, Biological, Mice, Models, 3T3-L1 Cells, Receptors, Adipocytes, CCAAT-Enhancer-Binding Protein-alpha, Animals, RNA, Small Interfering, Oligonucleotides/chemistry, Liver X Receptors, DNA-Binding Proteins/metabolism, Sterol Regulatory Element Binding Protein 1/metabolism, Nuclear Proteins, Cell Differentiation, CCAAT-Enhancer-Binding Protein-alpha/metabolism*, Plasmids/metabolism, Biological, Orphan Nuclear Receptors, DNA-Binding Proteins, PPAR gamma, Nuclear Proteins/chemistry*, Adipocytes/metabolism, NIH 3T3 Cells, RNA, Sterol Regulatory Element Binding Protein 1, PPAR gamma/metabolism*, Plasmids
Small Interfering/metabolism, Oligonucleotides, Phosphatidate Phosphatase, 610, Receptors, Cytoplasmic and Nuclear, Cytoplasmic and Nuclear/metabolism, Models, Biological, Mice, Models, 3T3-L1 Cells, Receptors, Adipocytes, CCAAT-Enhancer-Binding Protein-alpha, Animals, RNA, Small Interfering, Oligonucleotides/chemistry, Liver X Receptors, DNA-Binding Proteins/metabolism, Sterol Regulatory Element Binding Protein 1/metabolism, Nuclear Proteins, Cell Differentiation, CCAAT-Enhancer-Binding Protein-alpha/metabolism*, Plasmids/metabolism, Biological, Orphan Nuclear Receptors, DNA-Binding Proteins, PPAR gamma, Nuclear Proteins/chemistry*, Adipocytes/metabolism, NIH 3T3 Cells, RNA, Sterol Regulatory Element Binding Protein 1, PPAR gamma/metabolism*, Plasmids
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).115 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!