A Crucial Role of Sterol Regulatory Element-binding Protein-1 in the Regulation of Lipogenic Gene Expression by Polyunsaturated Fatty Acids

作者: Naoya Yahagi , Hitoshi Shimano , Alyssa H. Hasty , Michiyo Amemiya-Kudo , Hiroaki Okazaki

DOI: 10.1074/JBC.274.50.35840

关键词: BiochemistryTransgeneTranscription factorPolyunsaturated fatty acidFatty acidGene expressionSterol Regulatory Element Binding Protein 1Fatty acid synthaseRegulation of gene expressionBiology

摘要: Dietary polyunsaturated fatty acids (PUFA) are negative regulators of hepatic lipogenesis that exert their effects primarily at the level transcription. Sterol regulatory element-binding proteins (SREBPs) transcription factors responsible for regulation cholesterol, acid, and triglyceride synthesis. In particular, SREBP-1 is known to play a crucial role in lipogenic gene expression liver. To explore possible involvement suppression by PUFA, we challenged wild-type mice transgenic overexpressing mature form liver with dietary PUFA. mice, PUFA drastically decreased mature, cleaved protein nucleus, whereas precursor, uncleaved membranes was not suppressed. The decreases paralleled those mRNAs enzymes such as acid synthase acetyl-CoA carboxylase. did reduce amount protein, excluding possibility accelerated degradation SREBP-1. resulting sustained almost completely canceled mice. These results demonstrate suppressive effect on enzyme genes caused decrease which presumably due reduced cleavage precursor protein.

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