(P11-065-23) Micronutrients Added to a High-Fat Diet Reduce Its Effect on Expression of Genes in Tissues and Metabolic Pathways Associated With Insulin Resistance in Mice

Objectives:

Background: Obesity and its related metabolic dysfunctions, such as insulin resistance (IR), is associated with epigenetic alterations of gene expression. However, the relationship between micronutrients, epigenetic regulation of gene expression, and IR during the development of diet-induced obesity has yet to be defined.

Objective: To describe the impact of micronutrients on the expression of genes associated with IR during obesity development, before and after the addition of a designed multi-vitamin mineral mix (MVM) containing vitamins A, B1, B6, B12, and Zn, and Se.

Methods: Male C57BL/6J mice fed an HFD (60 kcal% fat) or a low-fat diet (LFD, 10% kcal fat) for 6 weeks post-weaning were randomized to 4 diets with or without added MVM, (n=12/group) for 9 weeks. Body weight (BW) was measured weekly. After 7 weeks on diets, an insulin tolerance test was performed. At termination, blood, liver, muscle, pancreas, and visceral fat pads were collected. Fasting serum glucose, insulin, C-peptide, leptin, adiponectin, hepatic triglyceride (TG) content, and one carbon (1-C) metabolites, as well as mRNA expression of genes involved in insulin secretion, clearance and signaling and adipose functions, were measured in the targeted tissues.

Results: Compared to LFD mice, HFD mice had higher BW and IR, fasting glucose, insulin, C-peptide, leptin, and hepatic TG concentrations, as well as dysregulated gene expression in all tissues and in hepatic 1-C metabolites (p < 0.05). However, the addition of MVM reduced these HFD-induced effects. In total, fat and MVM diets affected the expression of 22 preselected IR-associated genes with some being affected in more than one tissue. HFD-induced obesity reduced the expression of 27 genes across all tissues by an average of 47% and increased the expression of 5 by 230% (p < 0.05). MVM in the HFD increased the expression of 5 genes (74%, p< 0.05) in the eWAT. In the LFD groups, 2 genes were decreased in eWAT (44%), and one was increased in muscle (60%) due to MVM addition (p < 0.05). Fat content and MVM additions altered components of the 1-C cycle possibly favoring gene methylation.

Conclusions: Micronutrients have the potential to reduce IR in mice fed HFD, possibly through epigenetic regulation of gene expression in tissues and metabolic pathways associated with IR and obesity.

Funding Sources: Supported by various sponsors