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-RRFAS has many similarities to the PUFA-RR of L-pyruvate kinase gene while the proximal PUFA-RRFAS is comparable to the PUFA-RR of the S14 and stearoyl-CoA desaturase genes.
Original language | English (US) |
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Pages (from-to) | 1295-1299 |
Number of pages | 5 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 290 |
Issue number | 4 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
Keywords
- Fatty acid synthase
- Fatty acids
- Liver
- Nuclear factor-Y
- SREBP-1
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology