Decoding Therapeutic Pathways of Micronutriomics: Interaction of Vitamin E-Tocotrienol Rich Fraction (TRF) in Insulin-Resistant Zebrafish Larvae Model (Danio rerio)
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Abstract
Introduction: This study investigates the intricate crosstalk between type 2 diabetes mellitus (T2DM) and neurodegenerative disorders, an interaction that remains poorly understood. By exploring micronutrient-based therapeutic strategies, particularly the tocotrienol and tocopherol isomers of vitamin E, we aim to evaluate the potential of a “micronutriomic” approach using tocotrienol-rich fraction (TRF)-vitamin E in modulating these interconnected disease pathways. Method: The oxidative stress status was evaluated by malondialdehyde (MDA) and glutathione (GSH) levels. Next Generation Sequencing (NGS) of transcriptome profiling analysis were performed to study the regulation of gene involved in insulin signaling and neurodegeneration. Insulin resistance-zebrafish larvae were treated with TRF-vitamin E (1 ug/mL) or metformin (50 uM) as a positive control. Results: Both TRF-vitamin E and metformin significantly decreased MDA levels (p<0.05) and increased GSH levels (p<0.05). Differential expression analysis in TRF-vitamin E group indicates 202 downregulated genes and 639 upregulated genes from a total of 841 dysregulated genes. Metformin, revealed a total of 1,500 dsyregulated genes with 1,300 were upregulated and 200 were downregulated. A gene ontology study discovered that the TRF-vitamin E group’s dysregulated genes were considerably enriched in the calcium pathways. Conclusion: The findings suggest that MAPK-CA2+ signaling pathway may be an overlapping mechanism of action between TRF-vitamin E and metformin. Understanding these therapeutic pathwyas in TRF-vitamin E may provide into “micronutriomics” targeted strategies to restore this crosstalk diseases.
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