Adipokine-Enriched Adipose Extract Restores Skin Barrier and Ameliorates Inflammatory Dysregulation in Atopic Dermatitis Mice

Abstract

Background: Atopic dermatitis (AD) is a chronic dermatosis with high incidence worldwide characterized by skin barrier abnormalities and immune dysregulation. Conventional therapies are usually limited by side effects and high cost. Given the anti-inflammatory and repairing properties, adipokines are increasingly considered as promising therapeutic agents for dermatoses. Adipose collagen fragments (ACF), a novel adipokine-enriched product, may alleviate AD through modulating immune microenvironment and restoring skin barrier. Methods: ACF was extracted from adipose tissue via high-speed homogenization (10000 rpm/min, 1min) and centrifugation (3000 g, 3min). Ovalbumin-induced AD female BALB/c mice (6-week-old) were intradermally injected with 0.2ml of ACF or PBS (negative control), with normal mice being set as normal control (n=6). Dermatitis severity, inflammatory metrics (epidermal thickness, infiltrated mast cells, Th-type cytokines expression), and skin barrier-related metrics (transepidermal water loss [TEWL], skin barrier-related proteins expression) were evaluated after the AD induction period (day 50). ACF-derived bioactive components were also evaluated using proteomic analysis. Results: ACF-derived adipokines contained anti-inflammatory, skin barrier- and lipid biosynthesis-related components. ACF treatment decreased dermatitis severity (6.2±1.8, p<0.0001), epidermal thickness (25.7±12.8 μm, p=0.0045), infiltrated mast cells (31.3±12.4 cells/field, p=0.0475), and Th-type cytokines expression (INF-γ, TNF-α, IL-4, IL-4R, IL-13, and IL-17A; p<0.05) in AD skins. TEWL (29.8±13.8 g/m 2.h, p=0.0306) and skin barrier-related proteins expression (filaggrin: 14258±4375, p=0.0162; loricrin: 6037±1728, p=0.0010; claudin-1: 20043±6406, p=0.0420; ZO-1: 4494±1114, p=0.0134) were also improved. Conclusions: ACF improved AD in murine model by ameliorating inflammatory dysregulation and skin barrier defects (Graphical abstract, Supplementary Digital Content 1). Further validation is needed in more advanced animal models.