Polyunsaturated Fatty Acids Suppress Sterol Regulatory Element-binding Protein 1c Promoter Activity by Inhibition of Liver X Receptor (LXR) Binding to LXR Response Elements
In vitro study reveals polyunsaturated fatty acids suppress SREBP-1c promoter activity by competing with LXR ligands in HEK293 cells, highlighting dietary control of lipid synthesis.
Key Points
To investigate the precise molecular mechanism by which polyunsaturated fatty acids (PUFAs) suppress SREBP-1c promoter activity and inhibit cellular lipogenesis.
Conducted luciferase reporter gene assays in HEK293 cells transfected with SREBP-1c promoter and LXRE enhancer constructs.
Evaluated the effects of various fatty acids (arachidonic acid, EPA, DHA, linoleic acid, and saturated/monounsaturated fats) on wild-type and mutated/deleted LXRE promoters.
Assessed mechanism of action via gel shift mobility assays and LXR ligand-binding domain activation assays.
PUFAs strongly suppressed SREBP-1c promoter activity in a potency rank order of arachidonic acid > EPA > DHA > linoleic acid, whereas saturated and monounsaturated fatty acids showed minimal effects.
Deletion or mutation of two liver X receptor-responsive elements (LXREs) in the SREBP-1c promoter completely eliminated PUFA-mediated suppression.
PUFAs directly competed with LXR ligands in the LXR ligand-binding domain, preventing the LXR/retinoid X receptor heterodimer from binding to LXREs.