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

Abstract

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 antiinflammatory 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. ACF was extracted from adipose tissue by means of high-speed homogenization (10,000 rpm/min for 1 minute) and centrifugation (3000 g for 3 minutes). Ovalbumin-induced AD female BALB/c mice (6-week-old) were intradermally injected with 0.2 mL of ACF or phosphate-buffered saline (negative control), with normal mice being set as normal control ( n = 6). Dermatitis severity, inflammatory metrics (epidermal thickness, infiltrated mast cells, T helper cell [Th]-type cytokine expression), and skin barrier-related metrics (transepidermal water loss, skin barrier-related proteins expression) were evaluated after the AD induction period (day 50). ACF-derived bioactive components were also evaluated using proteomic analysis. ACF-derived adipokines contained antiinflammatory, 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 expression of Th-type cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-4, IL-4R, IL-13, and IL-17A [ P < 0.05]) in AD skins. Transepidermal water loss (29.8 ± 13.8 g/m 2 per hour [ P = 0.0306]) and skin barrier-related protein expression (filaggrin, 14,258 ± 4375 [ P = 0.0162]; loricrin, 6037 ± 1728 [ P = 0.0010]; claudin-1, 20,043 ± 6406 [ P = 0.0420]; and zonula occludens-1, 4494 ± 1114 [ P = 0.0134]) were also improved. ACF improved AD in a murine model by ameliorating inflammatory dysregulation and skin barrier defects. Further validation is needed in more advanced animal models. ACF is an injectable, adipose-derived collagen scaffold prepared from autologous harvested fat using fast and simple mechanical methods. ACF may reduce the limitations associated with health care regulatory issues and serve as a promising autologous therapeutic agent for skin disorders in clinics.