# A Novel Butyrate Derivative, Zinc Dibutyroyllysinate, Blunts Microphthalmia-Associated Transcription Factor Expression and Up-Regulates Retinol and Differentiation Pathway mRNAs in a Full-Thickness Human Skin Model

## TL;DR

A new compound, zinc dibutyroyllysinate, shows potential as a skincare ingredient by affecting genes related to skin health, pigmentation, and aging.

## Contribution

ZDL is a novel compound that uniquely modulates gene expression related to skin differentiation and melanin regulation.

## Key findings

- ZDL increases genes for epidermal differentiation and retinol metabolism while decreasing melanogenesis genes.
- ZDL boosts extracellular matrix proteins like collagen I and IV in a dose-dependent manner.
- ZDL reduces melanin secretion in melanocytes and does not replicate effects with alternative salts.

## Abstract

Lysine, butyric acid, and zinc play important roles in skin homeostasis, which involves aging, inflammation, and prevention of skin barrier disruption. This bioactivity spectrum is not replicated by any one topical compound currently in use. Our purpose in this study was to characterize a novel compound, zinc dibutyroyllysinate (ZDL), consisting of zinc with lysine and butyric acid moieties. We used RNA-seq to evaluate its effect on gene expression in a full-thickness skin model. We show that lysine alone has minimal effects on gene expression, whereas ZDL had greater transcriptional bioactivity. The effects of ZDL included an increased expression of genes promoting epidermal differentiation and retinol metabolism, along with a decreased expression of microphthalmia-associated transcription factor (MITF) and other melanogenesis genes. These effects were not replicated by an alternative salt compound (i.e., calcium dibutyroyllysinate). ZDL additionally led to a dose-dependent increase in skin fibroblast extracellular matrix proteins, including collagen I, collagen IV, and prolidase. Loss of melanin secretion was also seen in ZDL-treated melanocytes. These results provide an initial characterization of ZDL as a novel topical agent. Our findings support a rationale for the development of ZDL as a skincare ingredient, with potential applications for diverse conditions, involving melanocyte hyperactivity, pigmentation, inflammation, or aging.