Folic Acid Supplementation during the Juvenile-Pubertal Period in Rats Modifies the Phenotype and Epigenotype Induced by Prenatal Nutrition
ABSTRACT Prenatal nutritional constraint is associated with increased risk of metabolic dysregulation in adulthood contingent on adult diet. In rats, folic acid supplementation of a protein-restricted (PR) diet during pregnancy prevents altered phenotype and epigenotype in the offspring induced by the PR diet. We hypothesized that increasing folic acid intake during the juvenile-pubertal (JP) period would reverse the effects of a maternal PR diet on the offspring. Rats were fed a control (C) or PR diet during pregnancy and AIN93G during lactation. Offspring were weaned on d 28 onto diets containing 1 mg [adequate folate (AF)] or 5 mg [folic acid-supplemented (FS)] folic acid/kg feed. After 28 d, all offspring were fed a high-fat (18% wt:wt) diet and killed on d 84. As expected, offspring of PR dams fed the AF diet had increased fasting plasma triglyceride (TAG) and beta-hydroxybutyrate (betaHB) concentrations. The FS diet induced increased weight gain, a lower plasma betaHB concentration, and increased hepatic and plasma TAG concentration compared with AF offspring irrespective of maternal diet. PPARalpha and glucocorticoid receptor promoter methylation increased in liver and insulin receptor promoter methylation decreased in liver and adipose tissue in FS compared with AF offspring, with reciprocal changes in mRNA expression irrespective of maternal diet. These findings show that increased folic acid intake during the JP period did not simply reverse the phenotype induced by the maternal diet. This may represent a period of plasticity when specific nutrient intakes may alter the phenotype of the offspring through epigenetic changes in specific genes.
SourceAvailable from: tspace.library.utoronto.ca
[Show abstract] [Hide abstract]
ABSTRACT: Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity.Frontiers in Molecular Neuroscience 01/2014; 7:103. DOI:10.3389/fnmol.2014.00103
[Show abstract] [Hide abstract]
ABSTRACT: Many aging theories and their related molecular mechanisms have been proposed. Simple model organisms such as yeasts, worms, fruit flies and others have massively contributed to their clarification, and many genes and pathways have been associated with longevity regulation. Among them, insulin/IGF-1 plays a key and evolutionary conserved role. Interestingly, dietary interventions can modulate this pathway. Calorie restriction (CR), intermittent fasting, and protein and amino acid restriction prolong the lifespan of mammals by IGF-1 regulation. However, some recent findings support the hypothesis that the long-term effects of diet also involve epigenetic mechanisms. In this review, we describe the best characterized aging pathways and highlight the role of epigenetics in diet-mediated longevity.Biomolecular concepts 04/2015; DOI:10.1515/bmc-2014-0038