NF-Y involvement in the polyunsaturated fat inhibition of fatty acid synthase gene transcription

Margarita Teran-Garcia, Caterina Rufo, Manabu T. Nakamura, Steven D. Clarke, Timothy F. Osborne

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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 languageEnglish (US)
Pages (from-to)1295-1299
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume290
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Fatty acid synthase
  • Fatty acids
  • Liver
  • Nuclear factor-Y
  • SREBP-1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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