Skip to main content

Table 1 Evidence for a role of epigenetics in animal models of obesity separated by transmission type

From: Recent developments on the role of epigenetics in obesity and metabolic disease

Transmission type

Species

Experimental model

Phenotype affected

Epigenetic changes

Ref.

Intergenerational maternal effect

Sheep

Periconceptional undernutrition in normal and overweight ewes using artificial insemination and embryo transfer

Fat deposition and adrenal changes in offspring

Decreased expression of IGF2 and decreased DNA methylation of a proximal imprinting control region; changes in adrenal IGF2 DNA methylation; hypermethylation of pituitary glucocorticoid receptor

[14, 88–91]

Intergenerational maternal effect

Sheep

Maternal undernutrition prior to conception and during early gestation

Programming of obesity

Altered offspring histone methylation and acetylation in fetal hypothalamic energy regulating pathways

[20]

Intergenerational maternal effect

Sheep

Different maternal dietary energy sources during that last half of gestation

Late gestation fetal gene expression and DNA methylation from a variety of tissues

Changes in late gestation fetal DNA methylation of CpG islands associated with IGF2R and H19 in muscle and adipose tissue

[23]

Intergenerational maternal effect

Pig

Methylating micronutrient supplementation during gestation—impacts on F2

Back fat percentage, adipose tissue, and fat thickness at 10th rib, croup, and shoulder in F2

Differentially expressed metabolic genes in F2 liver and muscle, DNA methylation change in IYD

[31]

Intergenerational maternal effect

Mouse

Maternal low-protein diet during gestation and maternal diet restriction during gestation

Body weight, food intake, and adiposity

Altered germline DNA methylation of F1 adult males in a locus specific manner; changed expression and DNA methylation of LXRA in liver; demethylation of leptin promoter in adipocytes

[22, 26, 92]

Intergenerational maternal effect

Mouse

Maternal high-fat diet during gestation; maternal obesity model; maternal high-fat diet using a Glut4+/− genetic background; maternal diet-induced obesity

Offspring chromatin organization; metabolic syndrome in offspring unmasked by exposure to western diet; glucose intolerance, insulin resistance, hepatic steatosis; obesity; exacerbated metabolic syndrome in offspring; insulin levels, insulin resistance in adipose tissue

Changes in offspring hepatic histone marks H3K14ac and H3K9me3; changes in offspring hepatic gene expression and widespread subtle changes in cytosine methylation; DNA methylation change in PEG3 in spermatozoa of offspring; cell autonomous transmission of altered insulin signaling. Reduced IRS1 expression associated with elevated miR126

[21, 24, 28, 93]

Intergenerational maternal effect

Rat

Maternal diet restriction during gestation; suboptimal diet during early gestation

Catch up growth, obesity, and liver weight; T2D

Change in offspring liver IGF1 expression and IGF1 H3K4 methylation; decreased PPARA expression and increased DNA methylation in the PPARA promoter in liver; dhange in offspring growth hormone and PPARA expression and DNA methylation in liver; chromatin changes affecting enhancer/promoter interactions at HNF4A promoter in pancreatic islets from offspring

[17, 25, 29, 30]

Intergenerational maternal effect

Rat

Maternal overfeeding model during preconception and gestation

Adipogenesis, gene expression and reduced representation DNA methylation in offspring

Changes in gene expression and proximal DNA methylation in genes in lipogenic pathways of adipocytes from offspring

[16]

Intergenerational maternal effect

Macaque

Maternal high-fat diet during gestation

Altered expression of Npas2

Changes in offspring fetal liver chromatin mark H3K14ac in the NPAS2 promoter

[27]

Intergenerational paternal effect

Drosophila

Paternal overnutrition

Obesity in offspring

Chromatin (H3K9me3 and H3K27me3)-dependent reprogramming of offspring metabolic genes; a similar system may regulate obesity susceptibility and phenotypic variation in mice and humans

[33]

Intergenerational paternal effect

Mouse

Paternal low-protein diet

High cholesterol in offspring

Changes in hepatic gene expression and DNA methylation in offspring

[32]

Intergenerational paternal effect

Mouse

Intrauterine growth restriction

F1 offspring become obese and glucose intolerant with aging

F1 males show change in methylation of LXRA in sperm that is transmitted to somatic cells in the F2

[34]

Intergenerational paternal effect

Mouse

Paternal prediabetes

F1 has increased susceptibility to diabetes

F1 show changes in pancreatic gene expression and DNA methylation linked to insulin signaling. A large portion of these genes are also differentially methylated in sperm

[35]

Potential transgenerational effect

Mouse

Avy mouse—change in coat color and adult onset obesity through maternal transmission to the next generation; modulation by methyl donors and genistein during gestation.

Coat color and adult onset obesity in offspring

DNA methylation of a retrotransposon promoter adjacent to the agouti gene; evidence for germ line transmission of methylation status

[38–41, 94]

Effect resulting from direct exposure of adult

Mouse

High-fat diet

Weight, fasting glucose, glucose, and insulin tolerance tests; obesity

Differential DNA methylation at numerous sites in adipose tissue; changes in DNA methylation of metabolism-related genes in liver and oocytes

[43, 95]

  1. T2D type 2 diabetes