The Food Standards Agency undertakes a range of activities with the aim of improving the dietary health of the population and determining how best to communicate key messages to achieve dietary change. Activities include obtaining sound evidence from research and surveys, and seeking advice from independent experts. Work is also undertaken to inform and motivate the population about diet and to identify ways of improving their diet. The effectiveness of the work is monitored in order to inform future policy decisions and interventions and to understand cost implications.

The present paper is the introductory paper to a series of brief reviews representing the proceedings of a recent conference on ‘The biochemical basis for the health effects of exercise’ organized by the International Research Group on the Biochemistry of Exercise in conjunction with the Nutrition Society. Here the aim is to briefly review and highlight the main innovations presented during this meeting. The following topics were covered during the meeting: exercise signalling pathways controlling fuel oxidation during and after exercise; the fatty acid transporters of skeletal muscle; mechanisms involved in exercise-induced mitochondrial biogenesis in skeletal muscle; new methodologies and insights in the regulation of fat metabolism during exercise; muscle hypertrophy: the signals of insulin, amino acids and exercise; adipose tissue–liver–muscle interactions leading to insulin resistance. In these symposia state-of-the-art knowledge on how physical exercise exerts its effects on health was presented. The fast-growing number of identified pathways and processes involved in the health effects of physical exercise, which were discussed during the meeting, will help to develop tailored physical-activity regimens in the prevention of inactivity-induced deterioration of health.

The epidemic of ‘obesity’ in India is not appreciated because BMI underestimates the adiposity of Indians. Specific adiposity measurements are necessary for recognition of the adiposity of ‘thin’ Indians. The origin of this adiposity is only beginning to be understood. In addition to a possible genetic predisposition, intrauterine ‘programming’ might be responsible, although in the ‘thrifty phenotype’ hypothesis the adiposity of the ‘thin’ fetus has not been appreciated. Dutch men who faced ‘winter hunger’ during the first trimester of their in utero life have become more obese as adults. Low birth weight predicts central obesity in some studies, including studies in urban children. It has also been shown that small and thin Indian newborns (weight 2·7?kg and ponderal index 2·4?kg\m3) have poor muscle and visceral mass but higher adiposity for a given weight compared with white Caucasian babies. This body composition is influenced by maternal adiposity before pregnancy and by aspects of maternal nutritional intake and circulating nutrient concentrations during pregnancy. There are no strong paternal determinants of adiposity at birth. Adiposity may be an integral part of the orchestrated adjustments made to support ‘brain preservation’ during intrauterine growth, because brain tissue is predominantly fat. Increased nutrition in the face of a genetic predisposition or multigenerational undernutrition increases maternal insulin resistance in late pregnancy and promotes fetal adiposity even in absence of marked hyperglycaemia. Further research is necessary to define the role of specific nutrients and metabolites in the intrauterine processes promoting adiposity before maternal interventions to curtail the epidemic of obesity and diabetes are planned.

It is apparent from epidemiological studies that the timing of maternal nutrient restriction has a major influence on outcome in terms of predisposing the resulting offspring to adult obesity. The present review will consider the extent to which maternal age, parity and nutritional restriction at defined stages of gestation can have important effects on fat deposition and endocrine sensitivity of adipose tissue in the offspring. For example, in 1-year-old sheep the offspring of juvenile mothers have substantially reduced fat deposition compared with those born to adult mothers. Offspring of primiparous adult mothers, however, show increased adiposity compared with those born to multiparous mothers. These offspring of multiparous ewes show retained abundance of the brown adipose tissue-specific uncoupling protein 1 at 1 month of age. A stimulated rate of metabolism in brown fat of these offspring may act to reduce adipose tissue deposition in later life. In terms of defined windows of development that can programme adipose tissue growth, maternal nutrient restriction targetted over the period of maximal placental growth results in increased adiposity at term in conjunction with enhanced abundance of mRNA for the insulin-like growth factor-I and -II receptors. In contrast, nutrient restriction in late gestation, coincident with the period of maximal fetal growth, has no major effect on adiposity but results in greater abundance of specific mitochondrial proteins, i.e. voltage-dependent anion channel and/or uncoupling protein 2. These adaptations may increase the predisposal of these offspring to adult obesity. Increasing maternal nutrition in late gestation, however, can result in proportionately less fetal adipose tissue deposition in conjunction with enhanced abundance of uncoupling protein 1.

The National Diet and Nutrition Survey (NDNS) of adults aged 19–64 years, carried out in 2000–1, is part of the NDNS programme, a series of cross-sectional surveys aiming to provide detailed quantitative information on the diet, nutritional status and related characteristics of the British population. The programme is split into four surveys of different population age-groups, conducted at approximately three-yearly intervals. In the survey of adults food consumption data were collected from 1724 respondents using a 7 d weighed-intake dietary record. Other components included: height, weight, waist and hip circumference and blood pressure measurements; a 24 h urine sample; a blood sample; a record of physical activity. Results have been published in four volumes covering food consumption, energy and macronutrient intakes, micronutrient intakes and nutritional status, including physical measurements and physical activity. The results have shown that, based on a comparison of nutrient intakes with the UK dietary reference values, adults in Britain are generally getting sufficient nutrients from their diets. However, younger adults (particularly women) and those in lower socio-economic groups are more likely to have low micronutrient intakes and lower levels of some nutritional status indices. The proportion of food energy derived from total fat has fallen since the last survey of this age-group in 1986–7 and is close to the dietary reference value, while the proportion of energy derived from saturated fatty acids and non-milk extrinsic sugars exceeds the dietary reference values. The prevalence of overweight and obesity has increased since 1986–7 and physical activity levels are low.

Physical inactivity–gene interactions result in changes in gene expression, leading to phenotypic changes in the skeletal muscle cell. A subpopulation of those genes that show changes in expression during physical inactivity are candidates for the environment–gene interactions that cross a threshold of biological significance such that overt clinical disease occurs. AMP kinase, GLUT4 and myosin heavy chain IIx are proposed as candidates for physical inactivity-modulated genes that have an altered function that may trigger a crossing of a threshold to disease. Future experiments will be needed to test the validity of the ideas presented.

CHD is a multifactorial disease, caused by both genetic and environmental factors. The inherited 'defective' genes will vary from individual to individual, and any single mutation is likely to be making only a small contribution to risk. The context dependency, i.e. the importance of environmental factors in influencing genetic risk, is now becoming evident. Thus, a mutation may have a modest effect on risk in individuals who maintain a low environmental risk, but a major effect in a high-risk environment. Methods of analysing gene–environment interactions on CHD risk will be discussed and illustrated with several examples. APOE has three common alleles, ɛ2, ɛ3 and ɛ4. The ɛ4 allele has consistently been associated with CHD risk, which has been confirmed by meta-analysis. However, when the effect of genotype on risk was considered in smokers and non-smokers separately, risk in non-smokers was similar in all APOE genotypes. By comparison, in the smokers, ɛ3 homozygotes, as expected, had an approximately 2-fold higher risk, while for ɛ4 carriers there was a significantly greater than additive effect of genotype and smoking on risk (P ≫0.007). Thus, the impact of the ɛ4 allele on CHD risk appears to be confined to current smokers, an effect that has been confirmed in several studies. Another example is the interaction between the alcohol dehydrogenase 3 gene variant and alcohol consumption on CHD risk (P ≫0.001), showing the context dependency of the effect. Thus, the importance of considering environmental factors as potential genotype-risk modifiers has major public health implications.

Fe homeostasis is maintained by regulation of Fe absorption to balance largely unregulated body Fe losses. The majority of human subjects maintain relatively constant Fe stores; however, Fe deficiency and Fe overload are common conditions. Fe overload is frequently associated with mutations in genes of Fe metabolism. The present paper summarises present knowledge of these mutations as well as indicating other genes that animal studies have implicated as candidates for influencing body Fe stores.

Contraction-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism that leads to translocation of the GLUT4 glucose transporter to the muscle surface membrane from an intracellular storage site. Although the signalling events that increase glucose transport in response to muscle contraction are not fully elucidated, the aim of the present review is to briefly present the current understanding of the molecular signalling mechanisms involved. Glucose uptake may be regulated by Ca2+-sensitive contraction-related mechanisms, possibly involving Ca2+/calmodulin-dependent protein kinase II and some isoforms of protein kinase C. In addition, glucose transport may be regulated by mechanisms that reflect the metabolic status of the muscle, probably involving the 5′AMP-activated protein kinase. Furthermore, the p38 mitogen-activated protein kinase may be involved in activating the GLUT4 translocated to the surface membrane. Nevertheless, the picture is incomplete, and fibre type differences also seem to be involved.

Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30–40 μg/d, which is well below the current UK reference nutrient intake for adult men (75 μg/d) or women (60 μg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 μg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status.

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the ‘unilocular’ component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a ‘lipostatic’ role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

High circulating concentrations of leptin in obesity are associated with an apparent loss of its characteristic anorexic action within the hypothalamic region of the brain. Central insensitivity to leptin may therefore contribute to the aetiology of this disease, and an increased understanding of the underlying mechanisms will identify potential means of prevention and/or therapeutic targets. Seasonal animals such as sheep and Siberian hamsters (Phodopus sungorus) exhibit annual photoperiod-driven cycles of appetite and body weight. Increased food intake and weight gain in long days (summer) are associated with high circulating leptin, and decreased intake and weight loss in short days (winter) with low leptin. Critically, these cycles are associated with reversible changes in sensitivity to leptin. High sensitivity is seen in short days and relative insensitivity in long days, demonstrated both in sheep given leptin centrally via intracerebroventricular cannulas and in hamsters given leptin peripherally. In addition, primary hypothalamic appetite-regulating targets for leptin (i.e. neuropeptide Y, melanocortin and cocaine- and amphetamine-regulated transcript pathways) respond differently in these species to changes in circulating leptin and nutritional status induced by photoperiod as opposed to such changes induced by food restriction. Studies of seasonal animals will help to resolve causes of altered sensitivity to leptin and whether these changes reflect altered transport into the brain and/or altered signalling at the receptor or post-receptor level. Increased knowledge of the mechanism(s) and time-course for development and reversal of reduced central leptin sensitivity will provide new insights into the development and control of obesity.

Mammalian members of the cation diffusion facilitator (CDF) and zrt-, irt-like protein (ZIP) families of Zn transporters, initially identified in Saccharomyces cerevisiae and Arabidopsis thalania spp., have been cloned during the last 8 years and have been classified as families SLC30 and SLC39 respectively. The cloning of human Zn transporters ZnT-like transporter 1 (hZTL1)/ZnT5 (SLC30A5) and hZIP4 (SLC39A4) were major advances in the understanding of the molecular mechanisms of dietary Zn absorption. Both transporters are localised at the enterocyte apical membrane and are, therefore, potentially of fundamental importance in dietary Zn uptake. hZTL1 mediates Zn uptake when expressed in Xenopus laevis oocytes and hZIP4 is mutated in most cases of the inherited Zn deficiency disease acrodermatitis enteropathica. Localisation of hZTL1/ZnT5 at the apical membrane of the placental syncytiotrophoblast indicates a fundamental role in the transfer of Slc30 Zn to the foetus. Observations in rodent models indicate that in the intestine increased Zn availability increases expression of Zn transporters. Human intestinal Caco-2 cells show a similar response to increasing the Zn2+ concentration of the nutrient medium in relation to the expression of mRNA corresponding to several Zn transporters and that of ZnT1 (SLC30A1) and hZTL1/ZnT5 proteins. In the human placental cell line JAR, however, expression at the mRNA level of a number of Zn transporters is not modified by Zn availability, whilst ZnT1 and hZTL1/ZnT5 proteins are reduced under Zn-supplemented conditions. These differences between Caco-2 and JAR cells in Zn transporter gene responses to Zn supply may reflect the different extracellular Zn concentrations encountered by the corresponding cell types in vitro.

Fe homeostasis is considered in the context of the UK diet, using information on Fe intake and status from the National Diet and Nutrition Surveys. The importance of assessing Fe availability rather than total Fe intake is discussed. Dietary and host-related factors that determine Fe bioavailability (Fe utilised for Hb production) are reviewed using information from single-meal studies. When adaptive responses are taken into consideration, foods associated with higher Fe status include meat (haem-Fe and the ‘meat factor’) and fruits and fruit juice (vitamin C). Foods that may have a negative impact include dairy products (Ca), high-fibre foods (phytate) and tea and coffee (polyphenols), but the effects are more apparent in groups with marginal Fe deficiency, such as women of childbearing age. Analysis of dietary intake data on a meal-by-meal basis is needed to predict the influence of changing dietary patterns on Fe nutrition in the UK. Current information suggests that in the UK Fe deficiency is a greater problem than Fe overload.

The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated during exercise and muscle contraction as a result of acute decreases in ATP:AMP and phosphocreatine:creatine. Physical exercise increases muscle glucose uptake, enhances insulin sensitivity and leads to fatty acid oxidation in muscle. An important issue in muscle biology is to understand whether AMPK plays a role in mediating these metabolic processes. AMPK has also been implicated in regulating gene transcription and, therefore, may function in some of the cellular adaptations to training exercise. Recent studies have shown that the magnitude of AMPK activation and associated metabolic responses are affected by factors such as glycogen content, exercise training and fibre type. There have also been conflicting reports as to whether AMPK activity is necessary for contraction-stimulated glucose transport. Thus, during the next several years considerably more research will be necessary in order to fully understand the role of AMPK in regulating glucose transport in skeletal muscle.

The achievement of optimal folate status to prevent neural-tube defects, and possibly other diseases, is hindered by the well-recognised incomplete bioavailability of the natural folates found in foods compared with the synthetic vitamin, folic acid. Folate bioavailability from different foods is considered to be dependent on a number of factors, including the food matrix, the intestinal deconjugation of polyglutamyl folates, the instability of certain labile folates during digestion and the presence of certain dietary constituents that may enhance folate stability during digestion. There is conflicting evidence as to whether the extent of conjugation of polyglutamyl folate (in the absence of specific inhibitors of deconjugation in certain foods) is a limiting factor in folate bioavailability. Estimates of the extent of lower bioavailability of food folates compared with folic acid (relative bioavailability) show great variation, ranging anywhere between 10 and 98%, depending on the methodological approach used. The lack of accurate data on folate bioavailability from natural food sources is of particular concern in those countries in which there is no mandatory folic acid fortification, and therefore a greater reliance on natural food folates as a means to optimise status. Apart from the incomplete bioavailability of food folates, the poor stability of folates in foods (particularly green vegetables) under typical conditions of cooking can substantially reduce the amount of vitamin ingested and thereby be an additional factor limiting the ability of food folates to enhance folate status. A recent workshop convened by the Food Standards Agency concluded that gaining a better understanding of folate bioavailability in representative human diets is a high priority for future research.

The pyruvate dehydrogenase complex (PDC) has a key position in skeletal muscle metabolism as it represents the entry of carbohydrate-derived fuel into the mitochondria for oxidation. PDC is regulated by a phosphorylation–dephosphorylation cycle, in which the pyruvate dehydrogenase kinase (PDK) phosphorylates and inactivates the complex. PDK exists in four isoforms, of which the PDK4 isoform is predominantly expressed in skeletal and heart muscle. PDK4 transcription and PDK4 mRNA are markedly increased in human skeletal muscle during prolonged exercise and after both short-term high-intensity and prolonged low-intensity exercise. The exercise-induced transcriptional response of PDK4 is enhanced when muscle glycogen is lowered before the exercise, and intake of a low-carbohydrate high-fat diet during recovery from exercise results in increased transcription and mRNA content of PDK4 when compared with intake of a high-carbohydrate diet. The activity of pyruvate dehydrogenase (PDH) is increased during the first 2 h of low-intensity exercise, followed by a decrease towards resting levels, which is in line with the possibility that the increased PDK4 expressed influences the PDH activity already during prolonged exercise. PDK4 expression is also increased in response to fasting and a high-fat diet. Thus, increased PDK4 expression when carbohydrate availability is low seems to contribute to the sparing of carbohydrates by preventing carbohydrate oxidation. The impact of substrate availability on PDK4 expression during recovery from exercise also underlines the high metabolic priority given to replenishing muscle glycogen stores and re-establishing intracellular homeostasis after exercise.

The introduction of the process of nutritional screening into clinical standards has been driven by the increasing awareness of the prevalence of undernutrition in acute and primary care, along with its associated morbidity and mortality. However, the increasing prevalence of obesity in the general population suggests that an increased number of patients admitted to hospital will be obese. Increased morbidity has also been reported in the injured obese patient and may be associated with poor nutritional support. This situation may occur because the profound metabolic disturbances accompanying trauma in this group are not recognised, and subsequent feeding practices are inappropriate. Screening tools currently classify patients by using simple markers of assessment at the whole-body level, such as BMI. Subsequently, patients are identified as at risk only if they are undernourished. Such comparisons would by definition classify injured obese patients as at minimal or no nutritional risk, and they would therefore be less likely to be re-screened. This approach could result in potential increases in morbidity, length of rehabilitation and consequent length of hospital stay. It is likely that the identification of potential risk in obese injured patients goes beyond the measurement of such indices as BMI and percentage weight loss, which are currently utilised by the majority of screening processes.

Cu is an essential nutrient that is required for a broad range of cellular and molecular processes. Mammals have efficient systems to control Cu homeostasis that operate at the level of controlling uptake, distribution, sequestration and excretion of Cu. The study of diseases associated with disturbed Cu homeostasis has greatly enhanced our understanding of the molecular mechanisms involved in Cu metabolism. In man the liver is responsible for excreting excess Cu from the body by means of biliary secretion. Wilson disease is a severe human disorder characterized by Cu accumulation in the liver as a result of a deficiency in biliary Cu secretion. This disorder is caused by mutations in the gene that encodes a Cu-transporting P-type ATPase (ATP7B). The MURR1 gene was identified recently, and it was hypothesized that this gene is also essential for biliary Cu excretion and is presumed to act downstream of ATP7B. MURR1 is mutated in canine Cu toxicosis, a disorder with phenotypic characteristics similar to those of Wilson disease. MURR1 encodes a protein that is of unknown function and is without detectable sequence homology to known proteins. MURR1 is readily detected in all tissues and cell types, suggesting that it may exhibit a pleiotropic function in different organs, which may or may not be exclusively linked to Cu homeostasis. The use of genetic, biochemical and genomic tools, as well as the development of appropriate models in organisms other than dog, will allow the elucidation of the molecular and cellular function of MURR1 in relation to hepatic Cu homeostasis and biliary Cu excretion.