Integrated In Silico and In Vivo Analysis of Vitamin D3 Supplementation in Obesity and Diabetes

Abstract

Obesity and diabetes are interconnected metabolic disorders with a rising prevalence worldwide. Although vitamin D3 is known to regulate glucose metabolism and oxidative stress, its ability to inhibit digestive enzymes linked to adipogenesis has not been demonstrated. This study proposed that vitamin D3 possesses dual anti-obesity and antidiabetic activities by targeting pancreatic lipase, α-amylase, and α-glucosidase, and confirmed this hypothesis through in silico docking and in vivo experiments using Drosophila melanogaster. Docking simulations using AutoDock Vina showed that vitamin D3 had a stronger affinity for pancreatic lipase (−7.5 kcal/mol) than orlistat (−6.8 kcal/mol), with stable hydrophobic interactions at the catalytic sites. The D. melanogaster w1118 strain was reared on a high-fat diet (2% virgin coconut oil) supplemented with vitamin D3 (10 or 100 mM). The experimental groups (n = 20 flies per group, 5 replicates) were assessed for hemolymph glucose, locomotor activity, oxidative stress (NBT assay), and gene expression <trbl and sod1>. Data were analyzed using 1-way ANOVA with Tukey’s post-hoc test (p < 0.05). Vitamin D3 supplementation significantly reduced hemolymph glucose and ROS levels, improved crawling performance, and restored trbl and sod1 expression in HFD-fed flies. These effects were consistent with docking predictions, indicating that enzyme inhibition may underlie the observed metabolic benefits. In conclusion, vitamin D3 shows promising antiobesity and antidiabetic effects in a D. melanogaster model, supporting its role as a potential modulatory supplement. However, limitations such as the use of an invertebrate model, high compound concentrations, and the absence of mammalian or clinical validation highlight the need for further studies in higher organisms. HIGHLIGHTS Vitamin D3 exhibits strong in silico binding affinity to lipase and α-amylase. In vivo exposure to Vitamin D3 reduces cholesterol and glucose levels in Drosophila larvae Vitamin D3 promotes larval growth and locomotor activity under high-fat diet conditions Vitamin D3 upregulates the expression of trbl, sod1, and cat genes Vitamin D3 shows potential as a low-cost adjunctive therapy for obesity management GRAPHICAL ABSTRACT

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