Requirement of Fatty Acid Transport Protein 4 for Development, Maturation, and Function of Sebaceous Glands in a Mouse Model of Ichthyosis Prematurity Syndrome

Abstract

Background: Fatty acid transport protein 4 (FATP4) facilitates fatty acid uptake by converting fatty acids into active forms. Results: Reduced FATP4 in mice leads to dystrophic sebaceous glands and abnormal production and function of sebaceous gland lipid secretions. Conclusion: FATP4 plays crucial roles in the formation and function of lipid-secreting glands. Significance: Understanding how FATP4 regulates lipid metabolism is important in elucidating the pathogenesis and potential therapies for ichthyosis prematurity syndrome.

Linear ion-trap MSn with high-resolution MS reveals structural diversity of 1-O-acylceramide family in mouse epidermis

“…Mutations in SLC27A4, the gene encoding FATP4, are known to cause ichthyosis prematurity syndrome in humans (29,30). FATP4 is critical for development of fetal skin (31) and it has been hypothesized that lack of FATP4 in epidermal keratinocytes induces abnormal lipid metabolism in the epidermis that initiates the observed alterations in epidermal signaling pathways (32,33). It is still unclear whether the FATP4 gene plays a role in the synthesis of this complex Cer family.…”

<b>Immunohistochemical localization of fatty acid transporters and MCT1 in the sebaceous glands of mouse </b><b>skin </b>

“…FATP4 regulates the trafficking of very long-chain fatty acids necessary for the synthesis of sebum lipids. FATP4 may play crucial roles in the development and maturation of both sebaceous glands and meibomian glands as well as in the production of sebum (10). Although FATPs have been reported to be present in the plasma membrane (15), the present immunostaining at light and electron microscopic levels detected FATP4 mainly in the cytoplasm of sebaceous glands.…”

“…The colocalization of E-FABP with CD36 in the upper epidermis was observed in the present immunostaining, but the expression of E-FABP in the epidermis was fragmental (data not shown). FATP4 protein is immunohistochemically localized in the epidermis-mainly the granular layer-and in the sebaceous gland (10). In our immunostaining, the immunoreactivity for FATP4 in the skin was weak and restricted to some regions of the upper epidermis.…”

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis, and ocular integrity in mice

“…While several additional factors, including hair coat, skin blood circulation and regulation by the central nervous system, contribute to thermoregulation, it is likely that the observed defects are the result of depletion of sebum wax esters, which might lead to increased sebum fluidity and impaired fur waterproofing. Defects in water repulsion and thermoregulation have been previously described in several mouse lines lacking proteins involved in lipid synthesis (Chen et al, 2002;Lin et al, 2013;Westerberg et al, 2004;Zhang et al, 2014). However, in all mouse lines previously assessed, the defect was also present in the epidermis, making it impossible to discern between the roles played by epidermal and sebaceous lipids.…”

“…This resulted in considerable depletion of mature sebocytes, greatly impaired SG lipid content and a significant depletion of WE and TG in hair lipids. Together, WE and TG make up roughly 50% of lipid species in mouse hair (Lin et al, 2013). Considering the extensive ablation of mature sebocytes and the almost complete absence of lipids within the SG, it remains unclear why the chromatography did not reveal an even stronger reduction in overall hair lipids.…”