Eugenol inhibits preadipocyte differentiation and lipid accumulation via upregulating ATF3

The global prevalence of overweight status and obesity has increased considerably. Obesity is the common pathological basis of numerous diseases and a crucial triggering factor for diabetes. This study aimed to investigate the role of activating transcription factor 3 (ATF3) in the adipogenic process of adipocytes and the related compounds of Chinese medicine potentially targeting ATF3. The differentially expressed genes (DEGs) in high-fat diet (HFD) or overweight patients were identified by analyzing Gene Expression Omnibus (GEO) data profiles GSE112999, GSE112740, and GSE48964. qRT-PCR and western blot were conducted to detect the expression levels of related genes. Oil-red O staining was conducted to detect lipid droplet formation within 3T3-L1 adipocytes. Compounds that interacted with ATF3 were screened through the pharmacological database and analysis platform of the traditional Chinese medicine system. Furthermore, the eugenol effect on ATF3 expression was evaluated. ATF3 expression was increased in the adipose tissues of HFD mice and in clinically obese patients. Knock down of ATF3 promoted adipocyte lipid droplet formation, upregulated the protein levels of adipocyte markers (Fabp4 and PPARγ), elevated intracellular triglyceride (TG) levels, and activated the AKT signaling pathway. Eugenol effectively promoted ATF3 expression and inhibited adipocyte differentiation and adipogenesis. ATF3 expression was found to be elevated within the adipose tissues of overweight patients, whereas ATF3 knockdown promoted adipocyte differentiation and lipid accumulation by activating the PI3K/AKT signaling pathway. Therefore, ATF3 overexpression or supplementation with eugenol may be a potential method for overcoming obesity.