Fig. 3. Methyl supplementation prevents transgenerational increase in adult body weight.

In the study by Waterland et al. Agouti viable yellow (Avy) mice were employed to test the hypothesis that maternal obesity can induce a transgenerational amplification of obesity. The A^vy allele was passed through three generations of A^vy/a female mice and the cumulative effects on coat color and body weight were investigated. A potential mediation of transgenerational effects on body weight by DNA methylation was studied by analyzing two separate but contemporaneous populations of mice, one fed a standard diet and the other a methyl-supplemented diet capable of inducing DNA hypermethylation during development. The authors demonstrated the prevention of transgenerational increases in adult body weight by methyl supplementation. A Distribution of adult (P180) body weight of A^vy/a offspring by generation and group; n of the unsupplemented groups: 29 (F1), 36 (F2), and 88 (F3); n of the supplemented groups: 33 (F1), 62 (F2) and 117 (F3). The percentages in each panel indicate the proportion of offspring above 50 g (dotted line). Body weight was relatively constant in the supplemented group but increased transgenerationally in the unsupplemented group (P = 0.000006). B Methyl supplementation changed the association between maternal and offspring adult body weight. Adult body weight was measured at P180 for all dams and A^vy offspring in the study. In both the F2 and F3 generations, maternal adult body weight predicted offspring adult body weight in the unsupplemented group only. The P values of the analysis of covariance are provided. Reprinted by permission from Springer Nature, International Journal of Obesity, Methyl donor supplementation prevents transgenerational amplification of obesity, [57]. The figure is not included in the current article’s Creative Commons license.