Integration of physiological and molecular mechanisms of the developmental origins of adult disease: new concepts and insights.

It is now well established that an imbalance or reduction in the maternal diet either through pregnancy and lactation or at defined time points therein can have long-term effects on cardiovascular and metabolic health in the resulting offspring; the exact outcome varying greatly with the period of development or growth targeted. The EARly Nutrition programming - long-term follow up of Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST), or metabolic programming, project aims to determine the primary physiological and molecular mechanisms that cause long-term changes in both cardiovascular function and metabolic homeostasis. Thereafter, it also aims to examine nutritional interventions that could be adopted in order to overcome such complications. The present review summarises some of the more recent findings from a range of nutritional interventions in both small and large animals that are beginning to uncover novel pathways by which long-term health can be determined. These interventions include nutritional manipulations that can increase or decrease blood pressure in the resulting offspring as well as indicating their dissociation from adaptations in the kidney. Particular emphasis will be placed on growth during lactation in conjunction with the extent to which central and peripheral tissue adaptations can act to amplify, or protect, the offspring from later disease when born to nutritionally-manipulated mothers.