Integrated Omics Analysis Uncovers the Culprit behind Exacerbated Atopic Dermatitis in a Diet-Induced Obesity Model

• Published in: International journal of molecular sciences 2024-04, Vol.25 (8), p.4143
• Main Authors: Ahn, You Mee, Jung, Jeeyoun, Lee, So Min
• Format: Article
• Language: English
• Subjects: Advertising executives; Animals; Arachidonic acid; Arachidonic Acid - metabolism; Atopic dermatitis; Cytokines; Dermatitis; Dermatitis, Atopic - etiology; Dermatitis, Atopic - genetics; Dermatitis, Atopic - metabolism; Dermatitis, Atopic - pathology; Diet; Diet, High-Fat - adverse effects; Disease Models, Animal; Enzymes; Fatty acids; Genes; Lipid Metabolism - genetics; Lipidomics - methods; Lipids; Male; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; Obesity; Obesity - complications; Obesity - genetics; Obesity - metabolism; Phospholipids - metabolism; Plasma; Skin; Skin - metabolism; Skin - pathology; Unsaturated fatty acids
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25084143

Atopic dermatitis (AD), a chronic inflammatory skin disease, is exacerbated by obesity, yet the precise linking mechanism remains elusive. This study aimed to elucidate how obesity amplifies AD symptoms. We studied skin samples from three mouse groups: sham control, AD, and high-fat (HF) + AD. The HF + AD mice exhibited more severe AD symptoms than the AD or sham control mice. Skin lipidome analysis revealed noteworthy changes in arachidonic acid (AA) metabolism, including increased expression of , a key enzyme in AA generation. Genes for phospholipid transport ( ) and acyltransferase utilizing AA as the acyl donor ( ) were upregulated in HF + AD skin. Associations were observed between AA-containing phospholipids and skin lipids containing AA and its metabolites. Furthermore, imbalanced phospholipid metabolism was identified in the HF + AD mice, marked by excessive activation of the AA and phosphatidic acid (PA)-mediated pathway. This imbalance featured increased expression of , , and involved in PA generation, along with a decrease in genes converting PA into diglycerol (DG) and CDP-DG ( and ). This investigation revealed imbalanced phospholipid metabolism in the skin of HF + AD mice, contributing to the heightened inflammatory response observed in HF + AD, shedding light on potential mechanisms linking obesity to the exacerbation of AD symptoms.