The Effect of Micronutrients on Obese Phenotype of Adult Mice Is Dependent on the Experimental Environment.

The environment of the test laboratory affects the reproducibility of treatment effects on physiological phenotypes of rodents and may be attributed to the plasticity of the epigenome due to nutrient-gene-environment interactions. Here, we explored the reproducibility of adding a multi-vitamin-mineral (MVM) mix to a nutrient-balanced high-fat (HF) diet on obesity, insulin resistance (IR), and gene expression in the tissues of adult male mice. Experiments of the same design were conducted in three independent animal facilities. Adult C57BL/6J male mice were fed an HF diet for 6 weeks (diet induced-obesity model) and then continued for 9-12 weeks on the HF diet with or without 5-fold additions of vitamins A, B1, B6, B12, Zn, and 2-fold Se. The addition of the MVM affected body weight, fat mass, gene expression, and markers of IR in all three locations (p < 0.05). However, the direction of the main effects was influenced by the interaction with the experimental location and its associated environmental conditions known to affect the epigenome. In conclusion, MVM supplementation influenced phenotypes and expression of genes related to adipose function in obese adult male mice, but the experimental location and its associated conditions were significant interacting factors. Preclinical studies investigating the relationship between diet and metabolic outcomes should acknowledge the plasticity of the epigenome and implement measures to reproduce studies in different locations.

Methyl donor micronutrients, hypothalamic development and programming for metabolic disease.

Nutriture in utero is essential for fetal brain development through the regulation of neural stem cell proliferation, differentiation, and apoptosis, and has a long-lasting impact on risk of disease in offspring. This review examines the role of maternal methyl donor micronutrients in neuronal development and programming of physiological functions of the hypothalamus, with a focus on later-life metabolic outcomes. Although evidence is mainly derived from preclinical studies, recent research shows that methyl donor micronutrients (e.g., folic acid and choline) are critical for neuronal development of energy homeostatic pathways and the programming of characteristics of the metabolic syndrome in mothers and their children. Both folic acid and choline are active in one-carbon metabolism with their impact on epigenetic modification of gene expression. We conclude that an imbalance of folic acid and choline intake during gestation disrupts DNA methylation patterns affecting mechanisms of hypothalamic development, and thus elevates metabolic disease risk. Further investigation, including studies to determine translatability to humans, is required.