NF-Y Involvement in the Polyunsaturated Fat Inhibition of Fatty Acid Synthase Gene Transcription
Biochemical and Biophysical Research CommunicationsPublished 1 February 2002
Margarita Terán‐García, Caterina Rufo, Manabu Nakamura, Timothy F. Osborne, Steven D. Clarke
Citations44
SJR quartileQ2
SJR score0.75
SNIP0.56
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TL;DR
Dietary polyunsaturated fats (PUFA) reduce the hepatic content of SREBP-1 65-75%, and this is paralleled by a comparable decrease in the expression of fatty acid synthase (FAS) gene, which has led to the conclusion that PUFA inhibit lipogenic gene transcription by suppressing SRE BP-1 expression.
Abstract
Dietary polyunsaturated fats (PUFA) reduce the hepatic content of SREBP-1 65-75%, and this is paralleled by a comparable decrease in the expression of fatty acid synthase (FAS) gene. The close association between the nuclear content of SREBP-1 and FAS transcription has led to the conclusion that PUFA inhibit lipogenic gene transcription by suppressing SREBP-1 expression, but this conclusion is based upon correlative data. When in fact the SREBP-1/USF sites of the insulin response element of FAS were mutated, only 25% of the PUFA inhibition of FAS promoter activity was lost. On the other hand, mutating the -99/-93 NF-Y site reduced overall promoter activity 85%, and eliminated 50% of the PUFA suppression of FAS promoter activity. In addition, extended cloning and transfection-reporter assays revealed that the FAS gene contains a second PUFA response region (PUFA-RR) in the distal area of -7382/-6970. Interestingly, the distal PUFA-RR(FAS) has many similarities to the PUFA-RR of l-pyruvate kinase gene while the proximal PUFA-RR(FAS) is comparable to the PUFA-RR of the S14 and stearoyl-CoA desaturase genes.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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