Effects of post-weaning diet on metabolic parameters and DNA methylation status of the cryptic promoter in the Avy allele of viable yellow mice

Abstract

Mice carrying the Avy 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 Avy/a post-weaning mice were placed on one of three diets (AIN, and two lower calorie diets 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 Avy/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 Avy 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 = 0.003) 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 ≤ 0.001) with body weight of pseudoagouti mice. The findings indicate that post-weaning diet might influence interpretation of studies with Avy/a mice because IAP methylation patterns may be malleable in certain organs and influenced by post-weaning diet.

Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner

“…These findings are consistent with our previous observations made in rat models of gestational high multivitamin, high methyl vitamin, or high folic acid supplementation at 10x the control amounts diets (Cho et al 2015;Cho et al 2013a;Cho et al 2013b). In contrast, a methyl-supplemented post-weaning diet fed to viable yellow agouti mice failed to alter the offspring's coat colour and did not protect the yellow mice offspring D r a f t 19 against premature obesity or development of metabolic disease (Warzak et al 2015). However, this mouse study used offspring borne to dams fed a control diet, and therefore, the methyl-supplemented post-weaning diet was actually the mismatched diet.…”

Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring

“…A very powerful example of the potential effects of epigenetic modification comes from animal experiments involving the Agouti mouse. The wild-type Agouti gene encodes a paracrine-signaling molecule that produces either black or yellow fur [ 123 ]. When the agouti gene is in its normal methylated state, the coat is brown and the mouse has low risk of metabolic disease.…”

Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals

“…For example, Chronic high fat feeding in mice (from weaning to > 15 wk) altered patterns of DNA methylation within the promoter regions of the mu-opioid receptor in both the VTA and NAc in the brain ( Vucetic et al, 2011 , Pitman and Borgland, 2015 ). Likewise, post-weaning diet (high content of fat and carbohydrate) influence the hepatic intracisternal A particle (IAP) methylation patterns in mice ( Warzak et al, 2015 ). Furthermore, Postweaning high-fat diet predisposes the mouse offspring for obesity, and hypomethylation of proopiomelanocortin (POMC) promoter in the hypothalamus occurred ( Zheng et al, 2015 ).…”