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Arachidonic acid-dependent gene regulation during preadipocyte differentiation controls adipocyte potential

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J. Lipid Res.-2014-Nikolopoulou-2479-90.pdfPublished version2.02 MBAdobe PDFView/Open
Title: Arachidonic acid-dependent gene regulation during preadipocyte differentiation controls adipocyte potential
Authors: Nikolopoulou, E
Papacleovoulou, G
Jean-Alphonse, F
Grimaldi, G
Parker, MG
Hanyaloglu, AC
Christian, M
Item Type: Journal Article
Abstract: Arachidonic acid (AA) is a major PUFA that has been implicated in the regulation of adipogenesis. We examined the effect of a short exposure to AA at different stages of 3T3-L1 adipocyte differentiation. AA caused the upregulation of fatty acid binding protein 4 (FABP4/aP2) following 24 h of differentiation. This was mediated by the prostaglandin F2α (PGF2α), as inhibition of cyclooxygenases or PGF2α receptor signaling counteracted the AA-mediated aP2 induction. In addition, calcium, protein kinase C, and ERK are all key elements of the pathway through which AA induces the expression of aP2. We also show that treatment with AA during the first 24 h of differentiation upregulates the expression of the transcription factor Fos-related antigen 1 (Fra-1) via the same pathway. Finally, treatment with AA for 24 h at the beginning of the adipocyte differentiation is sufficient to inhibit the late stages of adipogenesis through a Fra-1-dependent pathway, as Fra-1 knockdown rescued adipogenesis. Our data show that AA is able to program the differentiation potential of preadipocytes by regulating gene expression at the early stages of adipogenesis.
Issue Date: 16-Oct-2014
Date of Acceptance: 7-Oct-2014
URI: http://hdl.handle.net/10044/1/54468
DOI: https://dx.doi.org/10.1194/jlr.M049551
ISSN: 0022-2275
Publisher: American Society for Biochemistry and Molecular Biology
Start Page: 2479
End Page: 2490
Journal / Book Title: Journal of Lipid Research
Volume: 55
Issue: 12
Copyright Statement: © 2014 by the American Society for Biochemistry and Molecular Biology, Inc. This is an open access article under a Creative Commons Licence 3.0 (https://creativecommons.org/licenses/by/3.0/)
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/H020233/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
adipogenesis
prostaglandins
cell signaling
metabolism
ACTIVATED-RECEPTOR-GAMMA
FOS-RELATED ANTIGEN-1
ADIPOSE CELL-DIFFERENTIATION
POLYUNSATURATED FATTY-ACIDS
PPAR-GAMMA
BINDING PROTEINS
3T3-L1 CELLS
EP4 RECEPTOR
DUAL ROLE
C-FOS
3T3-L1 Cells
Adipocytes, White
Adipogenesis
Animals
Arachidonic Acid
Calcium Signaling
Dinoprost
Down-Regulation
Fatty Acid-Binding Proteins
Gene Expression Regulation, Developmental
Kinetics
MAP Kinase Signaling System
Mice
Protein Kinase C
Proto-Oncogene Proteins c-fos
RNA Interference
RNA, Small Interfering
Receptors, Prostaglandin
Signal Transduction
Up-Regulation
0601 Biochemistry And Cell Biology
1101 Medical Biochemistry And Metabolomics
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer