Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Department of Human Health and Nutritional Sciences, College of Biological Science, University of Guelph, Guelph, Ontario, Canada.
Mol Nutr Food Res. 2023 Sep;67(18):e2300199. doi: 10.1002/mnfr.202300199. Epub 2023 Aug 1.
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.
肥胖和胰岛素抵抗（IR）与基因表达的表观遗传变化有关。然而，在饮食诱导肥胖发展过程中，微量营养素、基因表达的表观遗传调控与 IR 之间的关系尚未确定。我们的目的是描述在肥胖发展过程中，向饮食中添加微量营养素对 IR 及其相关基因的影响。
雄性 C57BL/6J 小鼠用高脂肪（HFD）或低脂肪（LFD）饮食喂养，或用含有维生素 A、B1、B6、B12 和 Zn、Se 的多种维生素矿物质混合物（MVM）喂养 9 周。与 LFD 小鼠相比，HFD 小鼠体重、IR、空腹血糖、胰岛素、C 肽、瘦素和肝甘油三酯浓度更高，肝脏、肌肉、胰腺和脂肪组织中的基因表达失调（p<0.05）。添加 MVM 可降低这些 HFD 诱导的作用。HFD 下调了与胰岛素调节和脂肪组织功能相关的 27 个基因，所有组织的平均下调幅度为 47%，上调了 5 个基因，上调幅度为 230%（p<0.001）。添加 MVM 可下调 HFD 喂养小鼠中的 5 个基因和上调 1 个基因。HFD 和 MVM 均改变了一碳代谢物。
向 HFD 添加微量营养素可降低肥胖和瘦小鼠的 IR，并改变相关基因表达。
