Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

Abstract

The skin is a flexible organ that forms a barrier between the environment and the body's interior; it is involved in the immune response, in protection and regulation, and is a dynamic environment in which skin lipids play an important role in maintaining homeostasis. The different layers of the skin differ in both the composition and amount of lipids. The epidermis displays the best characteristics in this respect. The main lipids in this layer are cholesterol, fatty acids (FAs) and ceramides. FAs can occur in free form and as components of complex molecules. The most poorly characterized FAs are very long-chain fatty acids (VLCFAs) and ultra long-chain fatty acids (ULCFAs). VLCFAs and ULCFAs are among the main components of ceramides and are part of the free fatty acid (FFA) fraction. They are most abundant in the brain, liver, kidneys, and skin. VLCFAs and ULCFAs are responsible for the rigidity and impermeability of membranes, forming the mechanically and chemically strong outer layer of cell membranes. Any changes in the composition and length of the carbon chains of FAs result in a change in their melting point and therefore a change in membrane permeability. One of the factors causing a decrease in the amount of VLCFAs and ULCFAs is an improper diet. Another much more important factor is mutations in the genes which code proteins involved in the metabolism of VLCFAs and ULCFAs—regarding their elongation, their attachment to ceramides and their transformation. These mutations have their clinical consequences in the form of inborn errors in metabolism and neurodegenerative disorders, among others. Some of them are accompanied by skin symptoms such as ichthyosis and ichthyosiform erythroderma. In the following review, the structure of the skin is briefly characterized and the most important lipid components of the skin are presented. The focus is also on providing an overview of selected proteins involved in the metabolism of VLCFAs and ULCFAs in the skin.

Changes in the Serum Fatty Acid Profile After Anhepatic Phase of Orthotopic Liver Transplantation Procedure

“…The most relevant changes in serum FA concentrations after reperfusion were observed in VLCFAs. VLCFAs are synthetized by hepatocytes in a multi-step process mediated by FA elongases ( Zwara et al, 2021 ). VLCFAs can be incorporated into other lipid structures, for example, sphingolipids, and they are degraded in peroxisomes.…”

Protective Actions of α-Tocopherol on Cell Membrane Lipids of Paraquat-Stressed Human Astrocytes Using Microarray Technology, MALDI-MS and Lipidomic Analysis

“…Moreover, the increase in ceramide production might be due to an activation of the de novo pathway, and this activation may lead to an increase in other sphingolipids by ceramides transformation, such as sphingomyelins [ 49 ] by the action of the SMS enzyme. However, the detected ceramides had ultra-long chain (ULC) fatty acids, the presence of which is related to inflammation and different diseases [ 54 ], including neurodegenerative disorders [ 54 , 55 ]. With α-tocopherol exposure, sphingomyelin adducts, such as SM 35:1; O2, either increase or appear as new species, with respect to the membranes from cells treated only with Paraquat.…”

Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation

“…11-Eicosenoic acid (C18:1) and C20:1 acid were increased, while the content of longer MUFA-C22:1, C24:1 was reduced in ApoE/LDLR -/-mice serum. The possible explanation of this observation may be the reduced activity of elongase 1 (ELOVL1) [40] that is responsible for elongation of very long-chain MUFAs, and this is another indication that FA metabolism in liver and adipose tissue requires further study in this experimental model. The examination of the role of FA content in improved cardiac and skeletal muscle function in this experimental model requires further studies.…”