Variations in human DNA, most frequently single-nucleotide polymorphisms (SNPs), can have functional consequences ranging from severe to none. Variations in outcome (phenotype) can be compared, from cystic fibrosis through haemochromatosis to general familial risks in, for example, colo-rectal cancer (CRC). Cystic fibrosis and haemochromatosis have severe phenotypes with high penetrance, with signs and symptoms always or mostly present; thus, they have been easy to identify from family studies. However, the familial risks that are known to contribute markedly to CRC are unknown. The sequencing of the human genome has now made possible the identification of these and other disease variants. Knowing the DNA sequence in an idealised individual adds little unless variants that increase (or decrease) disease risk from the norm can be identified. Such variants can be expected to be very common in the general population, but have low penetrance and only change risk to a limited extent. Many patients will not have the risk variant and many ‘normal’ patients will have the risk variant. Thus, very large case–control cohorts are essential. These case–control cohorts can be analysed at three different levels: (1) individual SNPs; (2) individual genes; (3) genome-wide analysis (GWA). Level 1 looks for case–control differences for specific SNPs. Alternatively, new technology can be applied to examine a range of SNPs within a gene to track differences in its regulation as well as in function. Finally, the whole genome with ≥0·5×106 SNPs could be marked. The first two approaches involve selecting ‘candidate’ SNPs or genes, while GWA looks for any variation in the genome that is enriched in the cases. All three approaches carry the certainty that significant associations will be found by statistical chance, for which correction must be made. This latter issue is helped by large numbers and by independent replication cohorts.

The primary role of the extensive and complex modern food legislation is to protect the consumer. Providing a framework for industry and enabling free trade are secondary aims. In the EU the 2006 Regulation on nutrition and health claims made on foods was adopted in December 2006. This Regulation defines detailed lists of permitted claims with precise conditions, requires foods making claims to meet specific nutrient profiles and requires the submission of a dossier for approval of new health claims. Nutrient profiles and an initial list of existing health claims will not be agreed until January 2009 and January 2010 respectively. The uncertainty about profiles and the initial list of claims as well as the prescriptive nature of the Regulation will have a major impact, some negative but some positive, on food innovation. Worldwide legislation on nutrition and health claims continues to develop. The current paper also provides an outline of some other key pieces of European legislation that affect food innovation. However, currently, all this legislation remains in development and up-to-date information can be sought from the reference material provided.

The obesity epidemic and its associated morbidity and mortality have led to major research efforts to identify mechanisms that regulate appetite. Gut hormones have recently been found to be an important element in appetite regulation as a result of the signals from the periphery to the brain. Candidate hormones include ghrelin, peptide YY, glucagon-like peptide-1 and gastric inhibitory polypeptide, all of which are currently being investigated as potential obesity treatments. Bariatric surgery is currently the most effective therapy for substantial and sustained weight loss. Understanding how levels of gut hormones are modulated by such procedures has greatly contributed to the comprehension of the underlying mechanisms of appetite and obesity. The present paper is a review of how appetite and levels of gastrointestinal hormones are altered after bariatric surgery. Basic principles of common bariatric procedures and potential mechanisms for appetite regulation by gut hormones are also addressed.

Internationally, socio-economic trends reinforce the complex physiological mechanisms that favour positive energy balance, leading to an accumulation of excess body weight and associated metabolic disorders. This so-called ‘obesogenic environment’ is characterised by increasing accessibility and affordability of energy-dense foods and declining levels of physical activity. In the face of such rapidly-rising obesity rates there is general consensus that strategies to address trends in weight gain must go forwards in the absence of complete evidence of cause or effective prevention strategy. Thus, strategy implementation and evaluation must contribute to, as well as be informed by, the evidence base. Social marketing research and practice has a track record that strongly indicates that it can contribute to both the evolving knowledge base on obesity and overweight control policy and the development of effective intervention strategies. Social marketing draws pragmatically on many disciplines to bring about voluntary behaviour change as well as requisite supporting policy and environmental change. Key objectives include: generating insights into the drivers of current behaviour patterns; important barriers to change; client-oriented approaches to new desirable diet and lifestyle choices. Social marketing recognises that target clients have the power to ensure success or failure of obesity control policies. Social marketing seeks to identify genuine exchange of benefits for target adopters of behaviour change and the advocates of change, and how they may be developed and offered within an appropriate relevant context. Social marketing adopts a cyclical approach of learning, strategic development and evaluation, and therefore is well placed to integrate with the multi-disciplinary demands of obesity prevention strategies.

Coeliac disease (CD), traditionally perceived as a rare childhood condition presenting with malabsorption, is instead an autoimmune multisystem disorder usually presenting in adulthood, affecting ⩾1% of the population and linked to the genetic expression of human leucocyte antigens (HLA) DQ2 and DQ8. Presentation occurs most often in the 40–60 years age-group, but potentially at any age. Symptoms attributable to the gut or to malabsorption may be mild, non-specific or absent; under one-third of patients have diarrhoea and almost half are overweight. Histological diagnosis no longer requires small intestine villous atrophy. The Marsh classification recognizes increased intraepithelial lymphocytes and crypt hyperplasia with intact villi as part of the gluten enteropathy spectrum, while some individuals have more subtle abnormalities identified only on electron microscopy. Serological testing for CD autoantibodies (to endomysium and tissue transglutaminase) has revolutionized diagnosis, shifting the process towards primary care. However, a substantial number of patients with CD are seronegative, particularly those without villous atrophy. The autoantibody to endomysium may be produced before histological change. The immune response to transglutaminase is crucial to the disease process. An exciting new development is the link between antibodies to organ-specific transglutaminases and clinical presentation; transglutaminases 2 (gut), 3 (skin) and 6 (nervous system). Negative testing for CD does not preclude its development later and HLA testing may allow ‘once and for all’ exclusion. In conclusion, an increasing proportion of patients with CD do not meet the ‘classic’ picture of malabsorption, positive serological testing and villous atrophy. Insisting on all these criteria for diagnosis will result in under diagnosis.

Over the past 20 years major advances have been made in the diagnosis and understanding of pathogenic mechanisms relating to coeliac disease. Recently-identified genetic markers support the immunological–inflammatory nature of the disease. It is hoped that these newly-identified genes will assist further dissection of the inflammatory pathways in coeliac disease and give insight into why certain individuals develop intolerance to dietary gluten.

All mammals are provided with two distinct adipose cells, white and brown adipocytes. White adipocytes store lipids to provide fuel to the organism, allowing intervals between meals. Brown adipocytes use lipids to produce heat. Previous descriptions have implied their localization in distinct sites of the body; however, it has been demonstrated that they are present together in many depots, which has led to the new concept of the adipose organ. In order to explain their coexistence the hypothesis of reversible physiological transdifferentiation has been developed, i.e. they are contained together because they are able to convert, one into the other. In effect, if needed the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ is associated with resistance to obesity and its related disorders. A new example of reversible physiological transdifferentiation of adipocytes is offered by the mammary gland during pregnancy, lactation and post-lactation stages. The gravidic hormonal stimulus seems to trigger a transdifferentiation of adipocytes into milk-producing and secreting epithelial glands. In the post-lactation period some of the epithelial cells of the mammary gland seem to transdifferentiate into adipocytes. Recent unpublished results suggest that explanted adipose tissue, as well as explanted isolated mature adipocytes, is able to transdifferentiate into glands with epithelial markers of milk-secreting mammary glands. These findings, if confirmed, seem to suggest new windows into the cell biology frontiers of adipocytes.

The exact aetiology of Crohn's disease remains unknown. The consensus is that the disease results from a complex interaction between genes, immunity and environmental factors. Diet is attractive, in theory, as an environmental risk factor in the aetiology of the disease. The epidemiological data, often impeded by methodological issues, have failed to confirm a direct link between pre-diet illness and the development of Crohn's disease. Once diagnosed, however, nutrition has an important role in disease management. Among the nutritional issues are malnutrition, weight loss and suboptimal nutritional status; these outcomes may be present at any stage of the disease but are likely to be overt during acute illness and hospitalisation. Malnutrition has been identified in approximately 40% of hospital admissions with Crohn's disease and is associated with higher mortality, longer hospital stays and higher healthcare costs. Patients in remission may indeed be overweight and appear to be influenced by the general population trends toward overweight and obesity. Irrespective of BMI, patients are at risk of micronutrient deficiencies. Vitamin D deficiency, for example, is common in Crohn's disease and has important implications for bone health. Moreover, newer evidence suggests that vitamin D has potential anti-inflammatory effects. Dietary approaches, in the form of enteral nutrition, have previously been shown to reduce inflammation and treat the active disease. Current guidelines now recommend that corticosteroids are more effective than enteral nutrition for treating adults. Enteral nutrition has important growth and developmental benefits and continues to be a recommended therapy for children with Crohn's disease.

Human obesity and its complications are an increasing burden in developed and underdeveloped countries. Adipose tissue mass and the mechanisms that control it are central to elucidating the aetiology of obesity and insulin resistance. Over the past 15 years tremendous progress has been made in several avenues relating to adipose tissue. Knowledge of the lipolytic machinery has grown with the identification of new lipases, cofactors and interactions between proteins and lipids that are central to the regulation of basal and stimulated lipolysis. The dated idea of an inert lipid droplet has been appropriately revamped to that of a dynamic and highly-structured organelle that in itself offers regulatory control over lipolysis. The present review provides an overview of the numerous partners and pathways involved in adipose tissue lipolysis and their interaction under various metabolic states. Integration of these findings into whole adipose tissue metabolism and its systemic effects is also presented in the context of inflammation and insulin resistance.

The vast majority of patients with coeliac disease will derive benefit from a gluten-free diet. However, some patients will not improve on the gluten-free diet or they will have a relapse of their symptoms. The present review will focus on this group of patients. Definitions for non-responsive coeliac disease and refractory coeliac disease will be provided. The most common reason for recurrent symptoms is continued gluten exposure. Other causes of persisting symptoms are discussed, including alternative causes of villous atrophy or co-existent pathology. Current literature is reviewed, including an initial investigation strategy for patients with persisting symptoms. A pragmatic management plan is described that can be initiated by any clinician. Finally, the current optimal investigational pathway for patients with refractory (or suspected refractory) coeliac disease is discussed and the reported effects of a number of therapeutic options are summarised. The aim of the present article is to provide clinicians with an up-to-date review of the literature in this clinical field and allow them to determine the most appropriate management strategy.

Sweat evaporation can be a key thermoregulatory mechanism and it causes a loss of water from all compartments of the body. Hypohydration can also develop with restricted fluid intake or with intake of diuretics. Hypohydration can affect physical and/or mental performance and/or have implications for dietary recommendations. A variety of different types and modes of exercise performance can be influenced by hydration state. Reviews of the published literature are currently most conclusive for endurance exercise. Dehydration equivalent to 2% body mass loss during exercise in a hot environment (31–32°C) impairs endurance performance, but when the exercise is performed in a temperate environment (20–21°C) a 2% body mass loss appears to have a lesser and inconsequential effect. In cold environments a body mass loss >2% may be tolerable for endurance exercise. There is a less conclusive picture as to the effects of hypohydration on other types of physical performance, including strength and power activities, team sports and the skills component of many sports, and for mental performance. A number of physiological mechanisms are responsible for the effects observed. Fluid consumption can be used to attenuate the development of a water deficit or to correct it. The composition and temperature of a drink and the volume and rate of its consumption can all influence the physiological responses to ingestion and can impact on exercise performance.