The Effect of Glycation on Epidermal Lipid Content, Its Metabolism and Change in Barrier Function

Abstract

Background/Aims: Advanced glycation end products, which are linked to both aging and hyperglycemia, cause marked functional and structural alterations in human skin. Though it is well known that the metabolism of glucose is closely associated with that of fatty acid (FA), sharing the same energy-yielding reaction pathways as glucose, its effect on the epidermis has been unclear so far. Methods: Content of ceramides, cholesterol and FA in a reconstructed epidermal model glycated by glyoxal was analyzed by high-performance thin-layer chromatography. FA species extracted from HaCaT keratinocytes was determined by gas chromatography/mass spectrometry. Regulation of FA synthesis was analyzed by real-time PCR. For physiological analysis, excised mouse skin was glycated using a vertical diffusion cell and used for the evaluation of barrier function by transepidermal water loss measurement and observation of penetration of sodium fluorescein. Results: Saturated FA content was significantly increased in glycated epidermis, and glycation upregulated mRNA expression of FA elongases 2 and 3 and FA synthase in HaCaT cells. Further, both inside-out and outside-in barriers were disrupted in glycated excised skin. Conclusion: Biological and physical change in the epidermis, especially upregulation of FA synthesis by glycation, contributed to barrier disruption, and inhibiting glycation may offer an effective treatment option for aged or glycated skin.

Age- and Diabetes-Related Changes in the Free Fatty Acid Composition of the Human Stratum Corneum

“…These result in increased oxidative stress and expression of redox-regulated genes and transcription factors, in changes regarding the composition of the extracellular matrix and in functional deficits of proteins [6,7]. These complex biochemical changes of epidermal micro milieu cause reduction in both keratinocytic proliferation and SC water content [8,9].…”

In vivo confocal Raman microscopic determination of depth profiles of the stratum corneum lipid organization influenced by application of various oils

“…intercellular lipids (ICL) of the stratum corneum (SC). The ICL matrix in the SC plays the key role in maintaining the skin barrier function, TEWL regulation, penetration of xenobiotics and drug delivery [8][9][10][11][12][13]. The skin barrier function is determined by the lateral organization of ICL [14][15][16], which can have three main forms: the orthorhombic structure which has less permeable and highly ordered states, the hexagonal structure which is medium permeable and more disordered than orthorhombic and the fluid state which is most permeable and disordered [17][18][19][20].…”

Hydrogen bound water profiles in the skin influenced by optical clearing molecular agents—Quantitative analysis using confocal Raman microscopy

“…As most concentrated in the skin, weakly and strongly bound water types are preferentially involved in the OCA-induced water flux in the skin, and thus, are responsible for optical clearing efficiency. barrier between the organism and environment, protecting the internal organs from external mechanical impact and penetration of pathogens [1]. Further important skin functions are regulation of the water loss, insulation, thermoregulation and so on [2,3].…”