Abstract
Obesity and insulin resistance (IR) are associated with epigenetic changes of gene expression. However, the relationship between micronutrients, epigenetic regulation of gene expression, and IR during development of diet-induced obesity has yet to be defined. Our objective is to describe the effect of micronutrient addition to diets on IR and its related genes during obesity development. Male C57BL/6J mice are fed a high-fat (HFD) or low-fat (LFD) diets with or without a multi-vitamin mineral mix (MVM) addition containing vitamins A, B1, B6, B12, and Zn, and Se for 9 weeks. Compared to LFD mice, HFD mice have higher body weight, IR, fasting glucose, insulin, C-peptide, leptin, and hepatic triglyceride concentrations, and dysregulated gene expression in liver, muscle, pancreas, and fat tissues (p < 0.05). The addition of MVM reduces these HFD-induced effects. HFD downregulates 27 genes associated with insulin regulation and adipose tissue function across all tissues by an average of 47% and upregulates five genes by 230% (p < 0.001). Adding MVM downregulates five genes and upregulates one in HFD-fed mice. Both HFD and MVM alter one-carbon metabolites. Addition of micronutrients to the HFD decreases IR and modifies associated gene expression in obese and lean mice.
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