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 ...

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The cardiovascular consequences of eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-specific intake were evaluated in vivo in a hyperinsulinemia (HI) model induced by dietary fructose intake. Wistar rats were fed a diet containing (or not for control) either EPA or DHA. The rise in blood pressure (BP), heart rate, and ECG were continuously monitored using an intra-abdominal telemetry system. The myocardial phospholipid fatty acid profile was significantly affected by DHA intake but less by EPA intake. The data indicated a reduced rise in BP in both DHA and EPA HI groups compared with controls. This result was confirmed by tail-cuff measurement after 5 wk [133.3 +/- 1.67 and 142.5 +/- 1.12 mmHg in n-3 polyunsaturated fatty acid (PUFA) and control groups, respectively], whereas n-3 PUFA did not affect BP in non-HI rats (116.3 +/- 3.33 mmHg). The heart rate was lower in the HI DHA group than in the other two dietary HI groups. Moreover, DHA induced a significantly shorter QT interval. It is concluded that the cardioactive component of fish oils is DHA through a mechanism that may involve the cardiac adrenergic system.

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AMP-activated protein kinase (AMPK) plays an important role in controlling energy homeostasis and is envisioned as a promising target to treat metabolic disorders. In the heart, AMPK is involved in short-term regulation and in transcriptional control of proteins involved in energy metabolism. Here, we investigated whether deletion of AMPK␣2, the main cardiac catalytic isoform, alters mitochondrial function and biogenesis. Body weight, heart weight, and AMPK␣1 expression were similar in control littermate and AMPK␣2 ؊/؊ mice. Despite normal oxygen consumption in perfused hearts, maximal oxidative capacity, measured using saponin permeabilized cardiac fibers, was ϳ30% lower in AMPK␣2 ؊/؊ mice with octanoate, pyruvate, or glutamate plus malate but not with succinate as substrates, showing an impairment at complex I of the respiratory chain. This effect was associated with a 25% decrease in mitochondrial cardiolipin content, the main mitochondrial membrane phospholipid that is crucial for complex I activity, and with a 13% decrease in mitochondrial content of linoleic acid, the main fatty acid of cardiolipins. The decrease in cardiolipin content could be explained by mRNA downregulation of rate-limiting enzymes of both cardiolipin synthesis (CTP:PA cytidylyltransferase) and remodeling (acyl-CoA:lysocardiolipin acyltransferase 1). These data reveal a new role for AMPK␣2 subunit in the regulation of cardiac muscle oxidative capacity via cardiolipin homeostasis. Diabetes 56: 786 -794, 2007