Maternal protein and folic acid intake during gestation does not program leptin transcription or serum concentration in rat progeny

Maternal nutrition during gestation influences the development of the fetus, thereby determining its phenotype, including nutrient metabolism, appetite, and feeding behavior. The control of appetite is a very complex process and can be modulated by orexigenic and anorexigenic mediators such as leptin, which is involved in the regulation of energy homeostasis by controlling food intake and energy expenditure. Leptin transcription and secretion are regulated by numerous factors, nutrition being one of them. The present study was designed to test whether maternal nutrition can permanently affect leptin gene transcription and leptin serum concentration in rat progeny. Moreover, we analyzed whether leptin expression and secretion in response to high-fat postweaning feeding depends on the maternal diet during gestation. Pregnant rats were fed either a normal protein, normal folic acid diet (the AIN-93 diet); a protein-restricted, normal folic acid diet; a protein-restricted, folic acid-supplemented diet; or a normal protein, folic acid-supplemented diet. After weaning, the progeny was fed either the AIN-93 diet or a high-fat diet. Neither maternal nutrition nor the postweaning diet significantly affected Lep transcription. High-fat feeding after weaning was associated with higher serum leptin concentration, but the reaction of an organism to the fat content of the diet was not determined by maternal nutrition during gestation. There was no correlation between Lep mRNA level and serum leptin concentration. Global DNA methylation in adipose tissue was about 30% higher in rats fed postnatally the high-fat diet (P < 0.01). Our study showed that the protein and folic acid content in the maternal diet had no significant programming effect on Lep transcription and serum leptin concentration in the rats

Epigenetic Epidemiology of Common Complex Disease: Prospects for Prediction, Prevention, and Treatment

As part of the PLoS Epigenetics Collection, Caroline Relton and George Davey Smith discuss the potential of epigenetics for the treatment and prevention of common complex diseases, including cancer

Epigenetics of obesity

Among different mechanisms that could lead to inter-individual differences in obesity susceptibility, epigenetics has emerged, in the last years, as a potentially very important contributor. The role of epigenetics in obesity may be considered by different points of view. Several nutritional factors are, in fact, known to influence epigenetic phenomena including DNA methylation, histone modifications, non-coding RNA expression and chromatin remodeling mechanisms, all of which significantly influence transcriptional regulatory pathways and phenotypic plasticity. Moreover, there are genes affecting metabolic processes related to weight control and obesity development whose expression is controlled by epigenetic mechanisms. A number of evidences suggests that epigenetic phenomena may be important in obesity development due to the dysregulation of known imprinted genes which have an essential role in normal growth and development and by modulating gene expression regulation through promoter DNA methylation at specific loci and histone modifications involved in obesity-linked metabolic pathways. Early life exposure to environmental/nutritional factors affecting epigenetics is also involved in obesity development. While some evidences are quite solid in this field, much is to be learned for the better understanding of epigenetic regulation in obesity and even more in terms of therapeutic prospectives. One of the objectives for the research in this novel area relies on the ability of defining epigenetic regulatory processes in genes involved in obesity and in a deeper knowledge on how epigenetic phenomena may be modulated by nutritional/environmental factors. Indeed, one of the main challenges is defining the epigenetic marks involved in obesity development and more specifically, to identify those which are potentially more susceptible to be modified by nutritional/environmental factors for specific preventive and therapeutic approaches

Chronic High-Fat Diet Drives Postnatal Epigenetic Regulation of μ-Opioid Receptor in the Brain

Opioid system dysregulation has been observed in both genetic and high-fat diet (HFD)-induced models of obesity. An understanding of the molecular mechanisms of MOR transcriptional regulation, particularly within an in vivo context, is lacking. Using a diet-induced model of obesity (DIO), mice were fed a high-fat diet (60% calories from fat) from weaning to >18 weeks of age. Compared with mice fed the control diet, DIO mice had a decreased preference for sucrose. MOR mRNA expression was decreased in reward-related circuitry (ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC)) but not the hypothalamus, important in the homeostatic regulation of feeding. DNA methylation is an epigenetic modification that links environmental exposures to altered gene expression. We found a significant increase in DNA methylation in the MOR promoter region within the reward-related brain regions. Methyl CpG-binding protein 2 (MeCP2) can bind methylated DNA and repress transcription, and DIO mice showed increased binding of MeCP2 to the MOR promoter in reward-related regions of the brain. Finally, using ChIP assays we examined H3K9 methylation (inactive chromatin) and H3 acetylation (active chromatin) within the MOR promoter region and found increased H3K9 methylation and decreased H3 acetylation. These data are the first to identify DNA methylation, MeCP2 recruitment, and chromatin remodeling as mechanisms leading to transcriptional repression of MOR in the brains of mice fed a high-fat diet