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Essential Fatty Acids and Epidermal Integrity

Philip W. Wertz, PhD; Donald C. Swartzendruber, PhD; William Abraham, PhD; Kathi C. Madison, MD; Donald T. Downing, PhD
[+] Author Affiliations

Accepted for publication May 15, 1987.

Read before the 36th Annual Symposium on the Biology of Skin ("Molecular Basis of Nutritional Dermatoses"), Salishan Lodge, Gleneden Beach, Ore, Oct 21, 1986.

Reprint requests to 270 Medical Laboratories, Department of Dermatology, University of Iowa College of Medicine, Iowa City, IA 52242 (Dr Wertz).


From the Department of Dermatology, Marshall Dermatology Research Laboratories, University of Iowa College of Medicine, Iowa City.


Arch Dermatol. 1987;123(10):1381-1384. doi:10.1001/archderm.1987.01660340149038
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• The intercellular spaces of the stratum corneum contain multilamellar lipid sheets derived from the extruded contents of lamellar granules. In the absence of linoleic acid, lamellar granules appear empty, and only fragmentary extracellular sheets are found. This defective differentiation is attributable to substitution of oleate for linoleate in O-acylsphingolipids. Normally, linoleate is ester-linked to 30- to 34-carbon ω-hydroxyacids, which, in turn, are amide-linked to sphingosine. Acylglucosylceramides, bearing a β-D-glucosyl moiety on the sphingosine, may provide the driving force for lamellar granule assembly. The ω-hydroxyacyl chains are long enough to span a lipid bilayer, while the linoleate inserts into an adjacent bilayer. This interaction could promote assembly of lamellar granules. It has also been proposed that acylceramides may stabilize the extracellular sheets by a similar mechanism. In addition, the horny cell has been found to possess a covalently bound lipid envelope consisting principally of ω-hydroxyacylsphingosines derived from O-acylsphingolipids.

(Arch Dermatol 1987;123:1381-1384)

REFERENCES

Attenborough D: Life on Earth . Boston, Little Brown & Co, 1979;.
Landmann L:  Lamellar granules in mammalian, avian, and reptilian epidermis . J Ultrastruct Mol Struct Res 1980;;72:245-263.
Wertz PW:  Lipids of keratinizing tissues , in Bereiter-Hahn J, Matoltsy AJ, Richards KS (eds): Biology of the Integument . New York, Springer-Verlag NY Inc, 1986;, vol 2, pp 815-823.
Winsor T, Burch GE:  Differential roles of layers of human epigastric skin on diffusion of water . Arch Intern Med 1944;;74:428-444.
Blank IH:  Cutaneous barriers . J Invest Dermatol 1965;;45:249-256.
Sweeney TM, Downing DT:  The role of lipids in the epidermal barrier to diffusion . J Invest Dermatol 1970;;55:135-140.
Squier CA:  The permeability of keratinized and nonkeratinized oral epithelium to horseradish peroxidase . J Ultastruct Mol Struct Res 1973;;43:160-177.
Breathnach AS, Goodman T, Stolinski C, et al:  Freeze fracture replication of cells in stratum corneum of human epidermis . J Anat 1973;;114:65-81.
Yardley HJ, Summerly R:  Lipid composition and metabolism in normal and diseased epidermis . Pharmacol Ther 1981;;13:357-383.
Wertz PW, Downing DT:  Ceramides of pig epidermis: Structure determination . J Lipid Res 1983;;24:759-765.
Long SA, Wertz PW, Strauss JS, et al:  Human stratum corneum polar lipids and desquamation . Arch Dermatol Res 1985;;277:284-287.
Elias PM, Brown BE:  The mammalian cutaneous permeability barrier: Defective barrier function in essential fatty acid deficiency correlates with abnormal intercellular lipid deposition . Lab Invest 1978;;39:574-583.
Holman RT:  Essential fatty acid deficiency . Prog Chem Fats Other Lipids 1968;;9:275-348.
Burr GO, Burr MM:  A new deficiency disease produced by the rigid exclusion of fat from the diet . J Biol Chem 1929;;82:345-367.
Houtsmuller UMT, Van Der Beek A:  Effects of topical application of fatty acids . Prog Lipid Res 1981;;20:219-224.
Elliott WJ, Morrison AR, Sprecher HW, et al:  The metabolic transformations of columbinic acid and the effect of topical application of the major metabolites on rat skin . J Biol Chem 1985;;260:1-6.
Hansen HS, Jensen B:  Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier: Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate, and α-linolenate . Biochim Biophys Acta 1985;;834:357-363.
Hansen HS, Jensen B, von Wettstein-Knowles P:  Apparent in vivo retroconversion of dietary arachidonic to linoleic acid in essential fatty acid-deficient rats . Biochim Biophys Acta 1986;; 878:284-287.
Sprecher HW:  Biochemistry of essential fatty acids . Prog Lipid Res 1981;;20:13-22.
Prottey C:  Investigation of functions of essential fatty acids in the skin . Br J Dermatol 1977;;97:29-38.
Elias PM, Brown BE, Ziboh VA:  The permeability barrier in essential fatty acid deficiency: Evidence for a direct role for linoleic acid in epidermal barrier function . J Invest Dermatol 1980;;74:230-233.
Gray GM, White RJ, Majer JR:  1-(3'-O-acyl)-β-glucosyl-1-(3'-O-acyl)-β-glucosyl-N-dihydroxypentatriacontadienoylsphingosine, a major component of the glucosylceramides of pig and human epidermis . Biochim Biophys Acta 1978;;528:127-137.
Wertz PW, Downing DT:  Acylglucosylceramides of pig epidermis: Structure determination . J Lipid Res 1983;;24:753-758.
Abraham W, Wertz PW, Downing DT:  Linoleate-rich acylglucosylceramides of pig epidermis: Structure determination by proton magnetic resonance . J Lipid Res 1985;;26:761-766.
Bowser PA, Nugteren DH, White RJ, et al:  Identification, isolation and characterization of epidermal lipids containing linoleic acid . Biochim Biophys Acta 1985;;834:419-428.
Schoephoerster RT, Wertz PW, Madison KC, et al:  A survey of polar and nonpolar lipids of mouse organs . Comp Biochem Physiol 1985;;82B:229-232.
Wertz PW, Cox PS, Squier CA, et al:  Lipids of epidermis and keratinized and nonkeratinized oral epithelia . Comp Biochem Physiol 1986;;83B:529-531.
Wertz PW, Downing DT, Freinkel RK, et al:  Sphingolipids of stratum corneum and lamellar granules of fetal rat epidermis . J Invest Dermatol 1984;;83:193-195.
Long VJW:  Variations in lipid composition at different depths in the cow snout epidermis . J Invest Dermatol 1970;;55:269-273.
Gray GM, Yardley HJ:  Different populations of pig epidermal cells: Isolation and lipid composition . J Lipid Res 1975;;16:441-447.
Matoltsy AG:  Keratinization . J Invest Dermatol 1976;;67:20-25.
Selby CC:  An electron microscope study of thin sections of human skin: II. Superficial cell layers of foot pad epidermis . J Invest Dermatol 1957;;29:131-149.
Odland GF:  A submicroscopic granular component in human epidermis . J Invest Dermatol 1969;;23:11-15.
Elias PM, Goerke J, Friend DS:  Mammalian epidermal barrier lipids: Composition and influence on structure . J Invest Dermatol 1977;;69:553-564.
Wertz PM, Downing DT:  Glycolipids in mammalian epidermis: Structure and function in the water barrier . Science 1982;;217:1261-1262.
Landmann L, Wertz PW, Downing DT:  Acylglucosylceramide causes stacking and flattening of liposomes: An analogy for assembly of the epidermal permeability barrier . Biochim Biophys Acta 1984;;778:412-418.
Lavker RM:  Membrane coating granules: The fate of the discharged lamellae . J Ultrastruct Mol Struct Res 1976;;44:79-86.
Landmann L:  The epidermal permeability barrier: Comparison between in vivo and in vitro lipid structures . Eur J Cell Biol 1984;;33:258-264.
Wertz PW, Cho ES, Downing DT:  Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat . Biochim Biophys Acta 1983;;753:350-355.
Wertz PW, Downing DT:  Covalent attachment of ω-hydroxyacid derivatives to epidermal macromolecules: A preliminary characterization . Biochem Biophys Res Commun 1986;; 137:992-997.
Odland GF, Reed TH:  Epidermis , in Zelickson AF (ed): Ultrastructure of Normal and Abnormal Skin . Philadelphia, Lea & Febiger, 1967;, pp 54-75.
Gray GM, King IA, Yardley HJ:  The plasma membrane of granular cells from pig epidermis: Isolation and lipid and protein composition . J Invest Dermatol 1978;;71:131-135.

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Attenborough D: Life on Earth . Boston, Little Brown & Co, 1979;.
Landmann L:  Lamellar granules in mammalian, avian, and reptilian epidermis . J Ultrastruct Mol Struct Res 1980;;72:245-263.
Wertz PW:  Lipids of keratinizing tissues , in Bereiter-Hahn J, Matoltsy AJ, Richards KS (eds): Biology of the Integument . New York, Springer-Verlag NY Inc, 1986;, vol 2, pp 815-823.
Winsor T, Burch GE:  Differential roles of layers of human epigastric skin on diffusion of water . Arch Intern Med 1944;;74:428-444.
Blank IH:  Cutaneous barriers . J Invest Dermatol 1965;;45:249-256.
Sweeney TM, Downing DT:  The role of lipids in the epidermal barrier to diffusion . J Invest Dermatol 1970;;55:135-140.
Squier CA:  The permeability of keratinized and nonkeratinized oral epithelium to horseradish peroxidase . J Ultastruct Mol Struct Res 1973;;43:160-177.
Breathnach AS, Goodman T, Stolinski C, et al:  Freeze fracture replication of cells in stratum corneum of human epidermis . J Anat 1973;;114:65-81.
Yardley HJ, Summerly R:  Lipid composition and metabolism in normal and diseased epidermis . Pharmacol Ther 1981;;13:357-383.
Wertz PW, Downing DT:  Ceramides of pig epidermis: Structure determination . J Lipid Res 1983;;24:759-765.
Long SA, Wertz PW, Strauss JS, et al:  Human stratum corneum polar lipids and desquamation . Arch Dermatol Res 1985;;277:284-287.
Elias PM, Brown BE:  The mammalian cutaneous permeability barrier: Defective barrier function in essential fatty acid deficiency correlates with abnormal intercellular lipid deposition . Lab Invest 1978;;39:574-583.
Holman RT:  Essential fatty acid deficiency . Prog Chem Fats Other Lipids 1968;;9:275-348.
Burr GO, Burr MM:  A new deficiency disease produced by the rigid exclusion of fat from the diet . J Biol Chem 1929;;82:345-367.
Houtsmuller UMT, Van Der Beek A:  Effects of topical application of fatty acids . Prog Lipid Res 1981;;20:219-224.
Elliott WJ, Morrison AR, Sprecher HW, et al:  The metabolic transformations of columbinic acid and the effect of topical application of the major metabolites on rat skin . J Biol Chem 1985;;260:1-6.
Hansen HS, Jensen B:  Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier: Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate, and α-linolenate . Biochim Biophys Acta 1985;;834:357-363.
Hansen HS, Jensen B, von Wettstein-Knowles P:  Apparent in vivo retroconversion of dietary arachidonic to linoleic acid in essential fatty acid-deficient rats . Biochim Biophys Acta 1986;; 878:284-287.
Sprecher HW:  Biochemistry of essential fatty acids . Prog Lipid Res 1981;;20:13-22.
Prottey C:  Investigation of functions of essential fatty acids in the skin . Br J Dermatol 1977;;97:29-38.
Elias PM, Brown BE, Ziboh VA:  The permeability barrier in essential fatty acid deficiency: Evidence for a direct role for linoleic acid in epidermal barrier function . J Invest Dermatol 1980;;74:230-233.
Gray GM, White RJ, Majer JR:  1-(3'-O-acyl)-β-glucosyl-1-(3'-O-acyl)-β-glucosyl-N-dihydroxypentatriacontadienoylsphingosine, a major component of the glucosylceramides of pig and human epidermis . Biochim Biophys Acta 1978;;528:127-137.
Wertz PW, Downing DT:  Acylglucosylceramides of pig epidermis: Structure determination . J Lipid Res 1983;;24:753-758.
Abraham W, Wertz PW, Downing DT:  Linoleate-rich acylglucosylceramides of pig epidermis: Structure determination by proton magnetic resonance . J Lipid Res 1985;;26:761-766.
Bowser PA, Nugteren DH, White RJ, et al:  Identification, isolation and characterization of epidermal lipids containing linoleic acid . Biochim Biophys Acta 1985;;834:419-428.
Schoephoerster RT, Wertz PW, Madison KC, et al:  A survey of polar and nonpolar lipids of mouse organs . Comp Biochem Physiol 1985;;82B:229-232.
Wertz PW, Cox PS, Squier CA, et al:  Lipids of epidermis and keratinized and nonkeratinized oral epithelia . Comp Biochem Physiol 1986;;83B:529-531.
Wertz PW, Downing DT, Freinkel RK, et al:  Sphingolipids of stratum corneum and lamellar granules of fetal rat epidermis . J Invest Dermatol 1984;;83:193-195.
Long VJW:  Variations in lipid composition at different depths in the cow snout epidermis . J Invest Dermatol 1970;;55:269-273.
Gray GM, Yardley HJ:  Different populations of pig epidermal cells: Isolation and lipid composition . J Lipid Res 1975;;16:441-447.
Matoltsy AG:  Keratinization . J Invest Dermatol 1976;;67:20-25.
Selby CC:  An electron microscope study of thin sections of human skin: II. Superficial cell layers of foot pad epidermis . J Invest Dermatol 1957;;29:131-149.
Odland GF:  A submicroscopic granular component in human epidermis . J Invest Dermatol 1969;;23:11-15.
Elias PM, Goerke J, Friend DS:  Mammalian epidermal barrier lipids: Composition and influence on structure . J Invest Dermatol 1977;;69:553-564.
Wertz PM, Downing DT:  Glycolipids in mammalian epidermis: Structure and function in the water barrier . Science 1982;;217:1261-1262.
Landmann L, Wertz PW, Downing DT:  Acylglucosylceramide causes stacking and flattening of liposomes: An analogy for assembly of the epidermal permeability barrier . Biochim Biophys Acta 1984;;778:412-418.
Lavker RM:  Membrane coating granules: The fate of the discharged lamellae . J Ultrastruct Mol Struct Res 1976;;44:79-86.
Landmann L:  The epidermal permeability barrier: Comparison between in vivo and in vitro lipid structures . Eur J Cell Biol 1984;;33:258-264.
Wertz PW, Cho ES, Downing DT:  Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat . Biochim Biophys Acta 1983;;753:350-355.
Wertz PW, Downing DT:  Covalent attachment of ω-hydroxyacid derivatives to epidermal macromolecules: A preliminary characterization . Biochem Biophys Res Commun 1986;; 137:992-997.
Odland GF, Reed TH:  Epidermis , in Zelickson AF (ed): Ultrastructure of Normal and Abnormal Skin . Philadelphia, Lea & Febiger, 1967;, pp 54-75.
Gray GM, King IA, Yardley HJ:  The plasma membrane of granular cells from pig epidermis: Isolation and lipid and protein composition . J Invest Dermatol 1978;;71:131-135.

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