Effects of a High-Fat Diet Exposure in Utero on the Metabolic Syndrome-Like Phenomenon in Mouse Offspring through Epigenetic Changes in Adipocytokine Gene Expression

Abstract

The links between obesity in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines such as leptin and adiponectin play important roles in glucose and lipid metabolism. Therefore, we examined whether the offspring from dams exposed to a high-fat diet during pregnancy (OH mice) exhibited hypertension, insulin resistance, and hyperlipidemia along with epigenetic changes in the expression of adipocytokine genes. OH mice were significantly heavier than the offspring of dams exposed to a control diet during pregnancy (OC mice) from 14 wk of age after an increased caloric intake from 8 wk. OH mice exhibited higher blood pressure and worse glucose tolerance than the OC mice at 24 wk. Total triglyceride and leptin levels were significantly higher and the adiponectin level was significantly lower in OH compared with OC mice at 12 wk of age. This was associated with changes in leptin and adiponectin expression in white adipose tissue. There were lower acetylation and higher methylation levels of histone H3 at lysine 9 of the promoter of adiponectin in adipose tissues of OH mice at 2 wk of age as well as at 12 and 24 wk of age compared with OC mice. In contrast, methylation of histone 4 at lysine 20 in the leptin promoter was significantly higher in OH compared with OC mice. Thus, exposure to a high-fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin, and leptin gene expression.

Human Adipocytes : Proteomic Approaches

“…Models of inheritance are published (e.g in [176,177] Regardless of heritability, histone variants and PTMs could be one of the factors facilitating the rapid adjustments of gene transcription to a changing environment. And regardless of whether they are the cause or the consequence, histone modifications have been associated with for example long term hyperglycemic memory after restoration of normoglycemia [181,182], and with altered transcription of adipokines after in-utero high fat diet exposure [183]. In paper II we showed that one specific histone modification is markedly downregulated in adipocytes from overweight individuals while another modification is increased in adipocytes from type 2 diabetic individuals, which indicates a relation between histone PTMs and metabolic state.…”

Life-long Maternal Cafeteria Diet Promotes Tissue-Specific Morphological Changes in Male Offspring Adult Rats

“…It is well recognized that maternal diet exerts epigenetic effects, such as DNA methylation, determining which genes are expressed in offspring and how the metabolism of fetus adapt to environment at birth and in adulthood (Masuyama andHiramatsu 2012, Dunford andSangster 2017). (Table II).…”

“…Maternal obesity can induce the metabolic programming of offspring in adulthood, culminating in obesity and its associated metabolic disorders (Howie et al 2009, White et al 2009, Li et al 2011, Daniel et al 2014, Jacobs et al 2014. The epigenetic molecular mechanisms, specifically DNA methylation, explain the relationship between maternal obesity induced by CAF diet and metabolic programming of offspring in adulthood (Masuyama and Hiramatsu 2012). Therefore, maternal weight during pregnancy is altered methylation patterns in the child's DNA and later infant adiposity (Dunford and Sangster 2017).…”

“…Therefore, maternal weight during pregnancy is altered methylation patterns in the child's DNA and later infant adiposity (Dunford and Sangster 2017). Thus, the maternal nutritional state by epigenetic mechanism determines which genes are expressed can enable the developing fetus to adapt to its environment at birth (Masuyama andHiramatsu 2012, Dunford andSangster 2017). In addition, the programmed metabolic phenotype, found in the offspring, could be exacerbated during growth, in particular when offspring are also exposed to a life-long obesogenic diet (Mucellini et al 2014).…”

Malnutrition périnatale et programmation métabolique

“…Au contraire, la descendance de mères obèses présente, elle, une modification de l'activité transcriptionnelle de facteurs adipogéniques (C/EBP , PPAR ) et de la leptine, qui est associée à des changements du niveau de méthylation des îlots CpG 2 de séquences régulant l'expression des gènes, et de marques d'histones pertinentes [6,12].…”