Effects of post-weaning diet on metabolic parameters and DNA methylation status of the cryptic promoter in the A(vy) allele of viable yellow mice.

Mice carrying the A(vy) allele are epigenetic mosaics. If the majority of cells have an active (demethylated) intracisternal A particle (IAP), mice have a yellow coat color and develop adult-onset obesity and diabetes, while mice whose mosaicism predominantly reflects an inactive (methylated) IAP are pseudoagouti (brown) and less prone to metabolic disease. Brown and yellow coat color A(vy)/a post-weaning mice were placed on one of three diets [AIN, and two lower-calorie diets National Institutes of Health (NIH) and methyl-supplemented, NIHMe] to determine whether coat color, weight gain, blood glucose and methylation of hepatic IAP became altered. None of the diets altered A(vy)/a mice coat color. NIHMe did not protect against increasing obesity or the usual onset of hyperglycemia in males. Nor did it promote increased methylation of A(vy) IAP in liver tissue. By contrast, AIN, despite its higher content of fat and carbohydrate and ability to promote greater weight gains than the NIH and NIHMe diets, protected males better against hyperglycemia than either the NIH or NIHMe diets. This diet led to a significantly reduced (~50%; P = .003) average methylation state of all CpG sites within the hepatic IAP for the pseudoagouti mice. On AIN, but not on the other diets, extent of hepatic IAP methylation was negatively correlated (R = 0.97, P ≤ .001) with body weight of pseudoagouti mice. The findings indicate that post-weaning diet might influence interpretation of studies with A(vy)/a mice because IAP methylation patterns may be malleable in certain organs and influenced by post-weaning diet.