Fibric acid derivatives like fenofibrate can modulate developmental gene expression patterns and selectively reinduce extinct genes such as LPL in adult rat liver.
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May influence rat hepatic gene expression; extends preclinical data but leaves open human translation or clinical relevance.
Liver lipoprotein lipase (LPL) and alpha-fetoprotein (AFP) gene expression show similar developmental patterns. Both mRNAs are abundantly expressed in neonatal rat liver and gradually disappear upon ageing. Treatment with fibric acid derivatives, such as fenofibrate, not only delays the developmental extinction of the LPL gene, but also increases LPL mRNA levels in neonatal rat liver. Similarly, the developmental extinction of the AFP gene in the liver is clearly delayed after fenofibrate. In adult rat liver, fibric acid derivatives transcriptionally reinduce a mRNA with similar size as LPL, but no effect on AFP mRNA was detected. Sequence comparison of clones isolated from a fenofibrate-induced cDNA library demonstrates that the fenofibrate-(re)induced mRNA in adult rat liver is encoding for LPL. The induction of LPL after fenofibrate is tissue-specific, since heart and adipose tissue LPL mRNA levels remain unchanged. In conclusion, fibric acid derivatives modulate developmental expression patterns in rat liver, and may selectively reinduce the expression of extinct genes in adult rat liver.
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Staels et al. (1992) studied this question.
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