
-   FABP5 relocates to the nucleus and potentially targets fatty acids to transcription factors, PPARbeta/delta, and PPARgamma in the nuclear lumen, thereby allowing PPARs to regulate lipid metabolism. The study hypothesized that the fatty acid-activated nuclear receptor PPAR links intracellular fatty acid levels to gene expression by binding to its response element (PPRE) in the promoter of a target gene [PMID: 12077340].

## Summary

In liver diseases and toxicities, the dysregulation of the Fabp5 gene plays a critical role in responding to altered metabolic demands and stress conditions [CS: 7]. For instance, in hepatocellular carcinoma (HCC), Fabp5 is overexpressed in response to high lipid overload [CS: 6]. This upregulation suggests a compensatory mechanism wherein Fabp5, as a transporter of fatty acids and active lipids, attempts to manage the excess lipid accumulation [CS: 7]. By facilitating the transport of these fatty acids into the nucleus, where they activate nuclear receptors like PPARbeta/delta, Fabp5 indirectly influences the expression of genes involved in lipid metabolism [CS: 7]. This mechanism can be seen as a response to restore metabolic homeostasis and to support the proliferative demands of cancer cells, as indicated by its association with poor prognosis in HCC [CS: 6].

In the context of liver injury due to endotoxin exposure, Fabp5 expression is linked to the modulation of inflammatory responses [CS: 6]. The gene's involvement in the pathway triggered by endotoxins and inflammatory mediators suggests its role in balancing the inflammatory state of the liver [CS: 5]. In FABP5 knockout mice, an increase in anti-inflammatory cytokines was observed, indicating that the normal function of Fabp5 might be to fine-tune the inflammatory response [CS: 8]. By influencing the biosynthesis of prostaglandin E2 (PGE2) and regulating PTGES induction via NF-kappa-B activation, Fabp5 can be seen as a mediator that balances pro-inflammatory and anti-inflammatory signals in the liver, aiming to maintain liver function and protect against excessive inflammatory damage [CS: 7].
