2001
DOI: 10.1074/jbc.m008973200
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Polyunsaturated Fatty Acids Suppress Hepatic Sterol Regulatory Element-binding Protein-1 Expression by Accelerating Transcript Decay

Abstract: The reduction in hepatic abundance of sterol regulatory element binding protein-1 (SREBP-1) mRNA and protein associated with the ingestion of polyunsaturated fatty acids (PUFA) appears to be largely responsible for the PUFA-dependent inhibition of lipogenic gene transcription. Our initial studies indicated that the induction of SREBP-1 expression by insulin and glucose was blocked by PUFA. Nuclear run-on assays suggested PUFA reduced SREBP-1 mRNA by post-transcriptional mechanisms. In this report we demonstrat… Show more

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Cited by 239 publications
(171 citation statements)
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“…The inability of triolinolein to increase SREBP-1 gene expression was not unexpected, because polyunsaturated fatty acids in general repress SREBP-1 gene expression and protein maturation in vitro and in vivo (52,56). The observed effects of the saturated fatty acids on SREBP-1 expression and maturation in SCD1Ϫ/Ϫ mice may suggest that in oleate deficiency saturated fatty acids (i.e.…”
Section: Discussionmentioning
confidence: 87%
“…The inability of triolinolein to increase SREBP-1 gene expression was not unexpected, because polyunsaturated fatty acids in general repress SREBP-1 gene expression and protein maturation in vitro and in vivo (52,56). The observed effects of the saturated fatty acids on SREBP-1 expression and maturation in SCD1Ϫ/Ϫ mice may suggest that in oleate deficiency saturated fatty acids (i.e.…”
Section: Discussionmentioning
confidence: 87%
“…Measurements of mRNA Degradation-Transcription of lipogenic genes in hepatocytes were activated by insulin and dexamethasone for 20 h and subsequently blocked by treatment with amanitin as described previously (33). Cells were then treated with either SB or vehicle solution as noted.…”
Section: Measurement Of Srebp-1cmentioning
confidence: 99%
“…Unsaturated fatty acid suppression of nuclear SREBP-1c levels is complex. In established cell lines, unsaturated fatty acids inhibit transcription of the SREBP-1 gene (15), enhance mRNA SREBP-1 turnover (16), and interfere with proteolytic processing of SREBPs (17). In primary hepatocytes, unsaturated fatty acids have little impact on SREBP-1c gene transcription (18,19) but enhance mRNA SREBP-1c turnover (16).…”
mentioning
confidence: 99%
“…In established cell lines, unsaturated fatty acids inhibit transcription of the SREBP-1 gene (15), enhance mRNA SREBP-1 turnover (16), and interfere with proteolytic processing of SREBPs (17). In primary hepatocytes, unsaturated fatty acids have little impact on SREBP-1c gene transcription (18,19) but enhance mRNA SREBP-1c turnover (16). Over-expression of nSREBP-1c in primary hepatocytes eliminates the polyunsaturated fatty acid (PUFA) effects on several lipogenic genes, indicating that SREBP-1c is a key target for PUFA action on de novo lipogenesis (19,20).…”
mentioning
confidence: 99%