Circadian gene signatures in the progression of obesity based on machine learning and Mendelian randomization analysis

Objective Obesity, a global health concern, is associated with a spectrum of chronic diseases and cancers. Our research sheds light on the regulatory role of circadian genes in obesity progression, providing insight into the immune landscape of obese patients, and introducing new avenues for therapeutic interventions. Methods Expression files of multiple datasets were retrieved from the GEO database. By 80 machine-learning algorithm combinations and Mendelian randomization analysis, we discovered the key circadian genes contributing to and protecting against obesity. Subsequently, an immune infiltration analysis was conducted to examine the alterations in immune cell types and their abundance in the body and to investigate the relationships between circadian genes and immune cells. Furthermore, we delved into the molecular mechanisms of key genes implicated in obesity. Results Our study identified three key circadian genes (BHLHE40, PPP1CB, and CSNK1E) associated with obesity. BHLHE40 was found to promote obesity through various pathways, while PPP1CB and CSNK1E counteracted lipid metabolism disorders, and modulated cytokines, immune receptors, T cells, and monocytes. Conclusion In conclusion, the key circadian genes (BHLHE40, CSNK1E, and PPP1CB) may serve as novel biomarkers for understanding obesity pathogenesis and have significant correlations with infiltrating immune cells, thus providing potential new targets for obese prevention and treatment.