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 | |
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 | |
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 | |
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 | |
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 | |
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 |