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Effects of fatty acids on hepatic gene expression
Prostaglandins, Leukotrienes, and Essential Fatty Acids
|February 1, 1995
Summary
Polyunsaturated fatty acids (PUFA) and peroxisomal proliferators (PP) impact liver gene expression. While both affect lipid metabolism, PUFA regulation of the S14 gene may not involve direct interaction with PPAR, a key PP mediator.
Area of Science:
- Biochemistry
- Molecular Biology
- Hepatology
Background:
- Polyunsaturated fatty acids (PUFA) significantly influence hepatic lipid metabolism by altering gene transcription.
- The S14 gene, encoding a lipogenic protein, serves as a model for understanding PUFA effects on gene expression.
- Peroxisomal proliferators (PP) also modulate liver lipid metabolism via gene expression, often through nuclear receptors like PPAR.
Purpose of the Study:
- To investigate the molecular mechanisms underlying PUFA and PP regulation of hepatic S14 gene expression.
- To determine if Peroxisome proliferator-activated receptor (PPAR) directly interacts with S14 gene regulatory elements.
Main Methods:
- Utilized cultured primary hepatocytes to study gene expression.
- Employed S14CAT fusion gene assays to assess transcriptional activity.
- Performed preliminary mapping and gel shift analysis to identify and characterize DNA-protein interactions.
Main Results:
- PUFA-regulated transcription factors target cis-regulatory elements in the S14 gene promoter (-220 to -80 bp).
- The potent PP, WY14,643, suppressed S14 mRNA levels and S14CAT activity in hepatocytes.
- PPAR did not directly bind to the identified S14 promoter or TRE elements, suggesting an indirect mechanism.
Conclusions:
- PUFA and PP may utilize shared cis-acting elements within the S14 promoter.
- PPAR-mediated regulation of S14 gene transcription by PUFA, if it occurs, does not involve direct binding to the S14 proximal promoter.