Adiponectin was recently reported to enhance human keratinocyte lipid synthesis via SIRT1 and nuclear hormone receptor signaling. In an effort to put adiponectin signaling into practical use to improve the skin barrier function, in vitro and in vivo mouse experiments were conducted to investigate the effect of synthesized adiponectin-derived peptide (Adi-pep D) on keratinocyte lipid synthesis and differentiation.
It was found that Adi-pep D induced adiponectin receptor activity by receptor-mediated endocytosis in HaCaT cells. Further, the expression of various lipid synthesis enzymes and the transcription factors related to the homeostasis of skin barrier function was examined in Adi-pep D-treated primary human keratinocytes. The expression of HMG CoA reductase and serine-palmitoyl transferase mRNA, and ABCA12 was increased. The expression of transcription factors SIRT1, LXRα, and SREBP was also increased. Nile red fluorescence staining showed an increase in the content of neutral lipid in Adi-pep-treated keratinocytes. Adi-pep D also increased the expression of epidermal differentiation marker (filaggrin/involucrin/loricrin) proteins in HaCaT cells.
We further evaluated whether the application of the synthetic peptide can reduce the deterioration of barrier function by topical application of very-potent corticosteroid on the murine skin. Functionally, the basal TEWL and SC hydration levels were not different, but the barrier recovery rate and integrity tended to improve, compared with those of the non-treated skin. When the epidermis was observed by transmission electron microscopy, the count and secretion of the lamellar body in the stratum corneum-granulosa interface were significantly increased.
These results suggest that the newly synthesized Adi-pep can help improve lipid synthesis, differentiation, and the skin barrier function recovery.