Nutritional programming of disease: unravelling the mechanism.

Nutritional programming is the process through which variation in the quality or quantity of nutrients consumed during pregnancy exerts permanent effects upon the developing fetus. Programming of fetal development is considered to be an important risk factor for non-communicable diseases of adulthood, including coronary heart disease and other disorders related to insulin resistance. The study of programming in relation to disease processes has been advanced by development of animal models, which have utilized restriction or over-feeding of specific nutrients in either rodents or sheep. These consistently demonstrate the biological plausibility of the nutritional programming hypothesis and, importantly, provide tools with which to examine the mechanisms through which programming may occur. Studies of animals subject to undernutrition in utero generally exhibit changes in the structure of key organs such as the kidney, heart and brain. These appear consistent with remodelling of development, associated with disruption of cellular proliferation and differentiation. Whilst the causal pathways which extend from this tissue remodelling to disease can be easily understood, the processes which lead to this disordered organ development are poorly defined. Even minor variation in maternal nutritional status is capable of producing important shifts in the fetal environment. It is suggested that these environmental changes are associated with altered expression of key genes, which are responsible for driving the tissue remodelling response and future disease risk. Nutrition-related factors may drive these processes by disturbing placental function, including control of materno-fetal endocrine exchanges, or the epigenetic regulation of gene expression.