Skin models with efficient skin barrier function are required for percutaneous absorption studies. The contribution of media supplementation with n-3 and n-6 polyunsaturated fatty acids (PUFAs) to the development of the skin barrier function of in vitro skin models remains incompletely understood. To investigate whether PUFAs, alpha-linolenic acid (ALA, n-3 PUFA) and linoleic acid (LA, n-6 PUFA), could enhance the impermeability of a three-dimensional reconstructed human skin model, skin substitutes were produced according to the self-assembly method using culture media supplemented with either 10 μM ALA or 10 μM LA. The impact of PUFAs on skin permeability was studied by using a Franz cell diffusion system to assess the percutaneous absorption of testosterone and benzoic acid. Our findings showed that ALA supplementation induced a decrease in the absorption of testosterone, while LA supplementation did not significantly influence the penetration of testosterone and benzoic acid under present experimental conditions. Both ALA and LA were incorporated into phospholipids of the skin substitutes, resulting in an increase in n-3 total PUFAs or n-6 total PUFAs. Collectively, these results revealed the under-estimated impact of n-3 PUFA supplementation as well as the importance of the n-6 to n-3 ratio on the formation of the skin barrier of in vitro reconstructed human skin models.
Keywords: lipidomics; polyunsaturated fatty acids; skin barrier function; skin substitutes; tissue engineering.
Conflict of interest statement
The authors declare no conflict of interest.
Deficiency of n-6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis-like pruritic skin inflammation in special diet-fed hairless mice.Exp Dermatol. 2013 Apr;22(4):272-7. doi: 10.1111/exd.12120. Exp Dermatol. 2013. PMID: 23528213
n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: A critical review.Crit Rev Food Sci Nutr. 2019;59(sup1):S116-S129. doi: 10.1080/10408398.2018.1544542. Epub 2018 Dec 22. Crit Rev Food Sci Nutr. 2019. PMID: 30580553 Review.
Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized Supplementation Approaches for the Prevention and Management of Human Diseases.Nutrients. 2017 Oct 25;9(11):1165. doi: 10.3390/nu9111165. Nutrients. 2017. PMID: 29068398 Free PMC article. Review.
Metabolism of linoleic and alpha-linolenic acids in cultured cardiomyocytes: effect of different N-6 and N-3 fatty acid supplementation.Mol Cell Biochem. 1996 Apr 12-26;157(1-2):217-22. doi: 10.1007/978-1-4613-1275-8_27. Mol Cell Biochem. 1996. PMID: 8739249
Anticonvulsant effects of linolenic acid are unrelated to brain phospholipid cell membrane compositions.Epilepsia. 2009 Jan;50(1):65-71. doi: 10.1111/j.1528-1167.2008.01723.x. Epub 2008 Jul 24. Epilepsia. 2009. PMID: 18657178