Metabolic imprinting, programming and epigenetics – a review of present priorities and future opportunities

Abstract

Metabolic programming and metabolic imprinting describe early life events, which impact upon on later physiological outcomes. Despite the increasing numbers of papers and studies, the distinction between metabolic programming and metabolic imprinting remains confusing. The former can be defined as a dynamic process whose effects are dependent upon a critical window(s) while the latter can be more strictly associated with imprinting at the genomic level. The clinical end points associated with these phenomena can sometimes be mechanistically explicable in terms of gene expression mediated by epigenetics. The predictivity of outcomes depends on determining if there is causality or association in the context of both early dietary exposure and future health parameters. The use of biomarkers is a key aspect of determining the predictability of later outcome, and the strengths of particular types of biomarkers need to be determined. It has become clear that several important health endpoints are impacted upon by metabolic programming/imprinting. These include the link between perinatal nutrition, nutritional epigenetics and programming at an early developmental stage and its link to a range of future health risks such as CVD and diabetes. In some cases, the evidence base remains patchy and associative, while in others, a more direct causality between early nutrition and later health is clear. In addition, it is also essential to acknowledge the communication to consumers, industry, health care providers, policy-making bodies as well as to the scientific community. In this way, both programming and, eventually, reprogramming can become effective tools to improve health through dietary intervention at specific developmental points.Imprinting or programming as a result of early life experience is becoming an accepted scientific phenomenon. Implicit in this is the concept of a 'stage of developmental plasticity, where specific conditions give rise to later life outcomes'. The most significant aspect is metabolic imprinting, in which maternal undernutrition, obesity and diabetes during gestation and lactation can contribute towards obesity in the offspring (1) . Other endpoints that seem to be affected by early life exposure include neurodevelopment and immune modulation.The concept of fetal growth affecting adult disease was explained by Barker (2,3) in his seminal papers. Programming later evolved to mean alterations in nutrition and growth at specific developmental points, resulting in long-term or even permanent effects (4) . Observation is the first step and the initial link between health and early diet is often found from epidemiological investigations. One of the most exemplary studies is the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (5) . This has been the source for a host of publications in which early diet is linked to later obesity and to other health endpoints, as outlined in Table 1.Other cohorts include the Helsinki study, which showed a link between prenatal and postnatal factors and ...

Position of the Academy of Nutrition and Dietetics: Nutrition and Lifestyle for a Healthy Pregnancy Outcome

“…Those conditions include obesity, cardiovascular disease, bone health, cognition, immune function, and diabetes. 13 Maternal weight gain during pregnancy outside the recommended range is associated with increased risk to maternal and child health. 4 While physiological responses to prenatal overnutrition result in poor health outcomes that emerge in childhood and adolescence, fetal undernutrition responses range from fetal survival to poor health outcomes emerging later in the offspring's adult life.…”

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…Some of these marks could be inherited from one or both carrier parents, and thus be detected early in life and, in some cases, steps might be taken to overcome them. Very interestingly, some epigenetic marks can be affected by environmental factors during in utero and perinatal stages, including maternal diet, uterine blood flow, lactation, and maternal nursing behavior (Hanley et al, 2010;Hanson et al, 2011a), so that they could be properly handled. Finally, others could be acquired during the process of aging due to metabolic, environmental and dietary factors that need to be thoroughly studied.…”

Early Influences of Nutrition on Postnatal Growth

“…These observations lead us to the conclusion that regulation of mTORC1 signaling by amino acids controls whole-body energy metabolism, bodyweight and body composition. Therefore, the current knowledge on the physiological mechanisms regulating metabolism, growth and related outcomes relevant for health indicate the large potential that improved nutritional practice during early life can have on long-term disease prevention and well-being, a concept widely known as early nutritional programming of life-long health [17][18][19][20][21][22][23]. Results of a recent randomized intervention trial in human infants demonstrate the powerful effects of modifying protein supply on metabolic and endocrine response as well as growth [24].…”