Untargeted Lipidomics Analysis to Discover Lipid Profiles and Biomarkers of Rabbit Acne Model and Reveal Action Mechanism of Isotretinoin

Liang Wu,1 Yunxia Zhu,1 Shengcai Zhu,1 Deng Zhang,1 Xiuping Wang,1 Zhen Xiao,2 Yanping Tan,3 Xiaoliang Ouyang,4 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of China; 4Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Xiaoliang Ouyang, Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email [email protected] Chunming Li, Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email [email protected]: Acne vulgaris (AV), a chronic inflammatory pilosebaceous disorder, affects 80– 90% of teenagers. This study aimed to discover lipid profiles and biomarkers of the rabbit ear acne model, and investigate the mechanism of isotretinoin in treating acne at the lipid level.Methods: Untargeted lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was performed to identify skin lipid metabolites in blank control (groups C), model group (group M) and isotretinoin group (group T). Multivariate statistical analysis was used to process the lipidomics data.Results: A total of 43 lipid classes comprising 6989 lipid species were identified from the mass spectrometry data. The orthogonal partial least squares discriminant analysis (OPLS-DA) model demonstrated significant separation in skin lipidomic profiles between group M and group C. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 299 significantly different lipid metabolites were identified. These lipid metabolites consisted mainly of ceramides (Cer) (53.85%), phosphatidylethanolamines (PE) (9.03%), phosphatidylcholines (PC)(5.35%), and sphingomyelin (SM)(4.01%). Combining with AUC ≥ 0.9 as the elected criteria, Cer (d18;1_24:0), zymosterol (ZyE)(33:5), Cer (t43:1), ZyE (33:6), ZyE (24:7), and ZyE (35:6) have “high” accuracy. Isotretinoin treatment normalized 25 lipid metabolites in the acne model.Conclusion: Our findings provide new insights into the role of lipid metabolism in the pathogenesis of acne and the action mechanism of isotretinoin.Keywords: acne vulgaris, lipidomics, isotretinoin, skin, animal model