Abstract
BACKGROUND: Acne vulgaris (AV) is a common inflammatory skin disease during adolescence. Metformin (MET) has recently been found to have the effects of regulating lipid disorders, suggesting its potential benefits in the treatment of AV patients. METHOD: Recruited 18 patients with moderate to severe AV, and then received MET treatment (AVM group) for a continuous period of 12 weeks, while 20 healthy controls (HC group) served as the control group. The Global Acne Grading System (GAGS) score and VISIA-CRTM imaging system were used to evaluate the severity of AV patients before and after treatment, and the serum lipid metabolomics differences were detected by liquid chromatograph mass spectrometer (LC-MS) before and after treatment. Multivariate statistical analysis of differentially expressed lipid metabolites was performed using partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The Mann-Whitney U test was used to analyze the differences in lipid metabolites between groups. Spearman correlation analysis was conducted to examine the correlation between differentially expressed serum lipid metabolites and the acne severity index. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to predict the metabolic pathways involved in the differentially expressed lipid metabolites in the AVM group. RESULTS: Compared to before treatment, the GAGS score (p < 0.001), red zone (p < 0.001) and Porphyrin (p < 0.01) indices of AV patients significantly improved after oral administration of MET. The results of PLS-DA and OPLS-DA indicated a clear separation in the composition of lipid metabolites between AV patients and the HC group; however, after MET treatment, the composition of lipid metabolites in AV patients showed a trend towards resembling that of the HC group. The 25 lipid metabolites with the most significant differences between AV patients and the HC group were all restored to the levels of the HC group after MET treatment. The Spearman correlation results showed that the serum PC (16:1/22:6) concentration in AV patients before treatment was positively correlated with the porphyrin area index (r = 0.47, p = 0.049). The KEGG analysis revealed 6 metabolic pathways that showed significant downregulation after treatment with MET. CONCLUSION: The therapeutic effect of MET on patients with moderate to severe AV may be achieved through the positive regulation of lipid metabolism. Its molecular mechanism may be related to the downregulation of inflammatory mediators associated with choline metabolism and arachidonic acid metabolism.