Insight into the Interaction Mechanism of Vitamin D against Metabolic Syndrome: A Meta-Analysis and In Silico Study

Abstract

As a dietary supplement or functional food additive, vitamin D (VD) deficiency may impact extra-skeletal functions associated with metabolic syndrome (MetS) risk factors. However, the precise effects and mechanisms of VD supplementation on dyslipidemia and insulin resistance in MetS subjects remain controversial. Here, we investigate potential therapeutic targets, pathways and mechanisms of VD against MetS through a comprehensive strategy including meta-analysis, network pharmacology analysis, molecular docking, dynamics simulations, and quantum chemical calculations. Our results reveal that VD supplementation significantly reduces triglyceride levels, fasting glucose, and insulin concentrations in subjects, thereby improving insulin homeostasis to some extent. We theoretically identify 14 core MetS-associated targets. Notably, VD exhibits substantial interactions with three targets (PPARγ, FABP4, and HMGCR) in the PPAR signaling pathway, indicating that VD can modulate this pathway. Van der Waals forces predominantly stabilize the complexes formed between VD and the three targets. Nonetheless, to provide valuable insights for personalized MetS management, further research is necessary to confirm our findings, emphasizing the importance of exploring genetic variability in VD response. In conclusion, our study contributes insights into the mechanisms of VD in preventing and treating MetS through dietary supplementation, promoting the development of VD-based functional foods or nutritious diets.