Role of lipids in the formation and maintenance of the cutaneous permeability barrier

Feingold, Kenneth R.; Elias, Peter M.

doi:10.1016/j.bbalip.2013.11.007

Cited by 383Advancements in Transdermal Drug DeliverySkin and Cellular Biology ResearchPlant Surface Properties and Treatments

Role of lipids in the formation and maintenance of the cutaneous permeability barrier

Feingold, Kenneth R., Elias, Peter M.·2014·Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

DOI 10.1016/j.bbalip.2013.11.007

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Abstract

The major function of the skin is to form a barrier between the internal milieu and the hostile external environment. A permeability barrier that prevents the loss of water and electrolytes is essential for life on land. The permeability barrier is mediated primarily by lipid enriched lamellar membranes that are localized to the extracellular spaces of the stratum corneum. These lipid enriched membranes have a unique structure and contain approximately 50% ceramides, 25% cholesterol, and 15% free fatty acids with very little phospholipid. Lamellar bodies, which are formed during the differentiation of keratinocytes, play a key role in delivering the lipids from the stratum granulosum cells into the extracellular spaces of the stratum corneum. Lamellar bodies contain predominantly glucosylceramides, phospholipids, and cholesterol and following the exocytosis of lamellar lipids into the extracellular space of the stratum corneum these precursor lipids are converted by beta glucocerebrosidase and phospholipases into the ceramides and fatty acids, which comprise the lamellar membranes. The lipids required for lamellar body formation are derived from de novo synthesis by keratinocytes and from extra-cutaneous sources. The lipid synthetic pathways and the regulation of these pathways are described in this review. In addition, the pathways for the uptake of extra-cutaneous lipids into keratinocytes are discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

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Many skin problems, including excessive exfoliation of the epidermis, are caused by a deficiency of GLA.
“Many skin problems, including excessive exfoliation of the epidermis, are also caused by a deficiency of GLA, which is formed from LA via an enzymatic reaction involving delta-6 desaturase [153,154,158,159].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [154]
Essential fatty acids play an important role in skin structure and function.
“EFAs also play an important role in skin structure and function.”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [154]
The symptoms of fatty acid deficiency include dryness of the epidermis, peeling, flabby skin, skin inflammation, an increased susceptibility to irritation and slower healing.
“The symptoms of fatty acid deficiency include dryness of the epidermis, peeling, flabby skin, skin inflammation, an increased susceptibility to irritation and slower healing.”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [154]
Owing to unsaturated fatty acids, which, alongside ceramides and cholesterol, are components of the intracellular cement, the skin can act as an effective barrier limiting TEWL, thus ensuring adequate hydration and protecting against external factors.
“Owing to unsaturated fatty acids, which, alongside ceramides and cholesterol, are components of the intracellular cement, the skin can act as an effective barrier limiting TEWL, thus ensuring adequate hydration and protecting against external factors [153,154,156].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [154]
A deficiency of linoleic acid, a component of ceramide 1, results in the dysfunction of the skin barrier and symptoms of dry skin.
“A deficiency of LA, a component of ceramide 1, which plays an important role in the cohesiveness of the intracellular cement, results in the dysfunction of the skin barrier and symptoms of dry skin.”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [154]

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Fatty acids are required for epidermal permeability barrier function.
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Impaired Epidermal Ceramide Synthesis Causes Autosomal Recessive Congenital Ichthyosis and Reveals the Importance of Ceramide Acyl Chain Length
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Integrity and Barrier Function of the Epidermis Critically Depend on Glucosylceramide Synthesis
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The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss
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The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss
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Retinal pathology and skin barrier defect in mice carrying a Stargardt disease-3 mutation in elongase of very long chain fatty acids-4.
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Authors: Feingold, K. R., & Elias, P. M.
Affiliations: San Francisco VA Medical Center (US)
Corresponding author: Feingold, Kenneth R.
ORCID: Elias, Peter M.
Venue: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Publisher: Elsevier BV
Published: 2014-03
Volume: 1841
Issue: 3
Pages: 280-294
ISSN: 1388-1981 (ISSN-L)
DOI: 10.1016/j.bbalip.2013.11.007
OpenAlex: W2123766496
Cited by: 383
References: 215
Citations by year: 2026: 19 · 2025: 23 · 2024: 26 · 2023: 31 · 2022: 32 · 2021: 37 · 2020: 42 · 2019: 35 · 2018: 30 · 2017: 29 · 2016: 41 · 2015: 26 · 2014: 12
FWCI: 3.32
Type: journal article
Language: en
Open access: closed
Locations: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Surface Properties and Treatments
Keywords: skin permeability barrier, stratum corneum, lamellar membranes, ceramide, cholesterol, free fatty acids, lamellar bodies, keratinocyte differentiation, glucosylceramide, beta-glucocerebrosidase, phospholipase, lipogenesis, epidermal lipids
MeSH terms: Epidermal Cells, Animals, Cell Differentiation, Epidermis, Humans, Lipids, Water-Electrolyte Balance, Keratinocytes, Lipid Metabolism

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Role of lipids in the formation and maintenance of the cutaneous permeability barrier

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