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

Highlights What are the main findings? In total, 14 core genes for vitamin D against MetS are obtained via enrichment analysis. Van der Waals forces are the main interactions to sustain vitamin D binding with targets. What is the implication of the main finding? Vitamin D could reduce triglycerides significantly and improve insulin resistance. Vitamin D might modulate the PPAR signaling pathway and inhibit bile secretion.Highlights What are the main findings? In total, 14 core genes for vitamin D against MetS are obtained via enrichment analysis. Van der Waals forces are the main interactions to sustain vitamin D binding with targets. What is the implication of the main finding? Vitamin D could reduce triglycerides significantly and improve insulin resistance. Vitamin D might modulate the PPAR signaling pathway and inhibit bile secretion.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 (PPAR gamma, 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.

Automated summary

The study reveals that vitamin D supplementation can significantly reduce triglyceride levels and improve insulin resistance in MetS. It identifies 14 core genes associated with MetS and highlights the potential of vitamin D to modulate the PPAR signaling pathway. The study emphasizes the need for further research to confirm these findings and explore genetic variability in response to vitamin D.