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Binding of polyunsaturated fatty acids to LXR α and modulation of SREBP‐1 interaction with a specific SCD1 promoter element
Author(s) -
Caputo Mariella,
De Rosa Maria Caterina,
Rescigno Tania,
Zirpoli Hylde,
Vassallo Antonio,
De Tommasi Nunziatina,
Torino Gaetano,
Tecce Mario Felice
Publication year - 2014
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3067
Subject(s) - sterol regulatory element binding protein , docosahexaenoic acid , polyunsaturated fatty acid , liver x receptor , eicosapentaenoic acid , lipogenesis , chemistry , biochemistry , arachidonic acid , transcription factor , fatty acid , enzyme , nuclear receptor , lipid metabolism , gene
Stearoyl‐CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, the mechanism of SCD1 regulation considering the involvement of two transcription factors: liver X receptor alpha (LXR α ) and sterol regulatory element‐binding protein‐1 (SREBP‐1), also investigating the effect of dietary polyunsaturated fatty acids (PUFAs) on this process. The analysis of SCD1 promoter allowed to identify a functional SREBP‐1 binding site (SRE 1). LXR α activation increased SCD1 protein level through upregulation of SREBP‐1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) were able to reduce SREBP‐1 binding to SCD1 promoter, while saturated stearic acid (SA, C18:0) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXR α . These data indicate a direct inhibitory interaction of PUFAs with LXR α , a consequent reduction of SREBP‐1 and of its binding to SCD1 promoter. This information provides a mechanism to explain the regulation of lipogenic pathways induced by PUFAs. Copyright © 2014 John Wiley & Sons, Ltd.