Early Life Nutrition and Lifelong Health - Derbyshire Local Medical ...

BMA Board of ScienceMost of the mechanisms have been investigated using animal models. 61-63 Studies in rats, mice,sheep, guinea pigs and in non-human primates all lend strong support to the developmentalorigins of health and disease hypothesis. Most notably, several characteristics of the offspringphenotypes arising from a range of maternal nutritional interventions, both by undernutrition andovernutrition, are shared across species. It has proved remarkably easy to demonstratecharacteristics equivalent to human disease, particularly features of the metabolic syndrome,through experimental manipulation of the diet of the pregnant animal or her offspring. The effectsinclude cardiovascular and renal dysfunction, insulin resistance, glucose intolerance, hyperphagia,altered stress responses and even preference for food high in fat and sugar in the offspring. 64Adulthood adiposity has also been induced. 65, 66 The behavioural effects on the offspring includereduced exploratory behaviour, activity levels and even impaired learning behaviour. 67 These animalmodels offer the potential for investigation of mechanisms, leading to suggestions for intervention.To date the most effective interventions reported have been supplementation of a low protein dietduring pregnancy in the rat with glycine 68, 69 or folate 70 or treatment of the pups neonatally withleptin. 71 The adverse effects on the offspring of feeding a high fat diet in pregnancy can bereduced by giving a statin to the pregnant animal in late gestation. 72 Animal investigations revealthat the transmission of risk factors can be passed to more than just the next generation. After anutritional challenge to animals during pregnancy effects were seen in their grand-offspring, evenwithout a further nutritional challenge. 73-75Key messageUnbalanced nutrition during development can lead to greater risks of chronic disease insuccessive generations.One of the most striking perceptions to arise from recent experimental work in this area is that theeffects of relatively modest dietary restriction or imbalance can affect offspring development andhave long-term consequences for health even when they are administered to the pregnant animalin either the periconceptional period, or in early pregnancy. At this time they do not invariablyaffect fetal growth or birth weight. They operate via effects on embryonic stem cell allocation 76or yolk sac function, 77 and have long-term effects on cardiovascular, endocrine and metabolicfunction. 78-82 Embryo transfer experiments also reveal long-term effects on these systems 83and this raises questions about the long-term consequences of assisted reproductive technologies.These observations are of general relevance because a high proportion of pregnancies are unplanned,and thus dietary and other effects can be exerted well before the woman realises that she is pregnant.Epigenetic mechanismsThe environmental effects on the embryo referred to above suggest in particular that epigeneticprocesses may be involved. The processes of phenotypic induction through developmental plasticityproduce integrated changes in a range of organs via epigenetic processes. The term ‘epigenetic’was coined by Waddington 84 in about 1942 to refer to the ways in which the developmentalenvironment can influence the mature phenotype. His work and that of others 85 on developmentalplasticity stemmed from observations that environmental influences during development couldinduce alternative phenotypes from a genotype. They establish a life-course strategy for meetingthe demands of the predicted later environment. 12 This explains why impaired early nutritionproduces a range of effects. These include alterations in cardiovascular and metabolic homeostasis,growth and body composition, cognitive and behavioural development, reproductive function,repair processes and longevity – some of which are associated with increased risk of chronic20Early life nutrition and lifelong health