Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP-1 interaction with a specific SCD1 promoter element.
Cell Biochem Funct
; 32(8): 637-46, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25264165
ABSTRACT
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 (LXRα) 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). LXRα activation increased SCD1 protein level through upregulation of SREBP-1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C226), eicosapentaenoic acid (EPA, C205) and arachidonic acid (AA, C204) were able to reduce SREBP-1 binding to SCD1 promoter, while saturated stearic acid (SA, C180) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXRα. These data indicate a direct inhibitory interaction of PUFAs with LXRα, 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estearoil-CoA Dessaturase
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Elementos de Resposta
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Proteína de Ligação a Elemento Regulador de Esterol 1
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Ácidos Graxos Insaturados
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Receptores Nucleares Órfãos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Biochem Funct
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Itália