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Updated: Apr 24, 2026

Quantification of Endothelial Fatty Acid Uptake using Fluorescent Fatty Acid Analogs
Published on: August 15, 2025
Fatty acid transport protein 1 can compensate for fatty acid transport protein 4 in the developing mouse epidermis
Meei-Hua Lin1, Jeffrey H Miner2
1Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA.
Insights
Fatty acid transport protein 1 (FATP1) can compensate for the loss of FATP4 in a mouse model of ichthyosis prematurity syndrome (IPS). This finding suggests FATP1 may offer a therapeutic strategy for improving skin barrier function in IPS patients.
Area of Science:
- Biochemistry
- Dermatology
- Genetics
Background:
- Fatty acid transport protein (FATP) 4 is crucial for skin barrier function, and its deficiency causes ichthyosis prematurity syndrome (IPS) in mice and humans.
- Mutations in SLC27A4, the gene encoding FATP4, lead to severe skin defects and neonatal lethality in IPS patients.
- Previous studies demonstrated that restoring FATP4 expression in keratinocytes can rescue the lethal phenotype in a mouse model.
Purpose of the Study:
- To investigate whether FATP1, a close homolog of FATP4, can functionally compensate for the absence of FATP4 in a mouse model of IPS.
- To explore the potential of FATP1 as a therapeutic target for treating skin abnormalities in IPS.
Main Methods:
- Generation of transgenic mice expressing FATP1 in suprabasal keratinocytes.
- Phenotypic analysis of Fatp4 mutant mice with FATP1 expression.
- Immunofluorescence microscopy to determine the subcellular localization of FATP1 and FATP4.
Main Results:
- Transgenic expression of FATP1 in suprabasal keratinocytes rescued the lethal phenotype and ameliorated the skin barrier defects in Fatp4 mutant mice.
- FATP1 was found to be localized in the same intracellular organelles as endogenous FATP4.
- These findings indicate functional overlap between FATP1 and FATP4.
Conclusions:
- FATP1 can functionally substitute for FATP4 in maintaining skin barrier integrity.
- FATP1 and FATP4 share overlapping substrate specificities, enzymatic activities, and biological functions.
- Increasing FATP1 expression in suprabasal keratinocytes presents a potential therapeutic strategy for IPS patients, possibly preventing atopic manifestations.
Abstract:
Fatty acid transport protein (FATP) 4 is one of a family of six FATPs that facilitate long- and very-long-chain fatty acid uptake. Mice lacking FATP4 are born with tight, thick skin and a defective barrier; they die neonatally because of dehydration and restricted movements. Mutations in SLC27A4, the gene encoding FATP4, cause ichthyosis prematurity syndrome (IPS), characterized by premature birth, respiratory distress, and edematous skin with severe ichthyotic scaling. Symptoms of surviving patients become mild, although atopic manifestations are common. We previously showed that suprabasal keratinocyte expression of a Fatp4 transgene in Fatp4 mutant skin rescues the lethality and ameliorates the skin phenotype. Here we tested the hypothesis that FATP1, the closest FATP4 homolog, can compensate for the lack of FATP4 in our mouse model of IPS, as it might do postnatally in IPS patients. Transgenic expression of FATP1 in suprabasal keratinocytes rescued the phenotype of Fatp4 mutants, and FATP1 sorted to the same intracellular organelles as endogenous FATP4. Thus, FATP1 and FATP4 likely have overlapping substrate specificities, enzymatic activities, and biological functions. These results suggest that increasing expression of FATP1 in suprabasal keratinocytes could normalize the skin of IPS patients and perhaps prevent the atopic manifestations.
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