Early life nutrition and neuroendocrine programming

Alterations in the nutritional environment in early life can significantly increase the risk for obesity and a range of development of metabolic disorders in offspring in later life, effects that can be passed onto future generations. This process, termed development programming, provides the framework of the developmental origins of health and disease (DOHaD) paradigm. Early life nutritional compromise including undernutrition, overnutrition or specific macro/micronutrient deficiencies, results in a range of adverse health outcomes in offspring that can be further exacerbated by a poor postnatal nutritional environment. Although the mechanisms underlying programming remain poorly defined, a common feature across the phenotypes displayed in preclinical models is that of altered wiring of neuroendocrine circuits that regulate satiety and energy balance. As such, altered maternal nutritional exposures during critical early periods of developmental plasticity can result in aberrant hardwiring of these circuits with lasting adverse consequences for the offspring. There is also increasing evidence around the role of an altered epigenome and the gut-brain axis in mediating some of the central programming effects observed. Further, although such programming was once considered to result in a permanent change in developmental trajectory, there is evidence, at least from preclinical models, that programming can be reversed via targeted nutritional manipulations during early development. Further work is required at a mechanistic level to allow for identification for early markers of later disease risk, delineation of sex-specific effects and pathways to implementation of strategies aimed at breaking the transgenerational transmission of disease. This article is part of the special Issue on 'Cross Talk between Periphery and the Brain'.

Automated summary

Changes in early life nutrition can have significant effects on the risk of obesity and metabolic disorders in later life, which can be passed on to future generations. This process, known as developmental programming, plays a role in the origins of health and disease. Early nutritional compromise can lead to adverse health outcomes in offspring, with the potential for exacerbation by a poor postnatal nutrition environment. The mechanisms underlying programming are not yet fully understood, but altered neuroendocrine circuits that regulate satiety and energy balance have been identified as a common feature in preclinical models.