Nutrigenetics and nutrigenomics are promising multidisciplinary fields that focus on studying the interactions between nutritional factors, genetic factors and health outcomes. Their goal is to achieve more efficient individual dietary intervention strategies aimed at preventing disease, improving quality of life and achieving healthy aging. Our studies, and those of many other investigators, using population-based and intervention studies have found evidence for interactions between dietary factors, genetic variants and biochemical markers of CVD. Now, the characterization of individuals who may respond better to one type of dietary recommendation than another can be begun. Thus, a low-fat low-cholesterol strategy may be particularly efficacious in lowering the plasma cholesterol levels of those subjects carrying the apoE4 allele at the APOE gene. HDL-cholesterol (HDL-C) levels are also modulated by dietary, behavioural and genetic factors. It has been reported that the effect of PUFA intake on HDL-C concentrations is modulated by an APOA1 genetic polymorphism. Thus, subjects carrying the A allele at the –75 G/A polymorphism show an increase in HDL-C with increased intakes of PUFA, whereas those homozygotes for the more common G allele have the expected lowering of HDL-C levels with increased intake of PUFA. Variability at the hepatic lipase gene is also associated with interactions between intake of fat and HDL-C concentrations that could shed some light on the different abilities of certain ethnic groups to adapt to new nutritional environments. This knowledge should lead to successful dietary recommendations partly based on genetic factors that may help to reduce cardiovascular risk more efficiently than the current universal recommendations.

Intracellular Ca2+plays an important role in skeletal muscle excitation–contraction coupling and also in excitation–transcription coupling. Activity-dependent alterations in muscle gene expression as a result of increased load (i.e. resistance or endurance training) or decreased activity (i.e. immobilization or injury) are tightly linked to the level of muscle excitation. Differential expression of genes in slow- and fast-twitch fibres is also dependent on fibre activation. Both these biological phenomena are, therefore, tightly linked to the amplitude and duration of the Ca2+transient, a signal decoded downstream by Ca2+-dependent transcriptional pathways. Evidence is mounting that the calcineurin–nuclear factor of activated T-cells pathway and the Ca2+/calmodulin-dependent kinases (CaMK) II and IV play important roles in regulating oxidative enzyme expression, mitochondrial biogenesis and expression of fibre-type specific myofibrillar proteins. CaMKII is known to decode frequency-dependent information and is activated during hypertrophic growth and endurance adaptations. Thus, it was hypothesized that CaMKII, and possibly CaMKIV, are down regulated during muscle atrophy and levels of expression of CaMKIIα, -IIβ, -IIγ and -IV were assessed in skeletal muscles from young, aged and denervated rats. The results indicate that CaMKIIγ, but not CaMKIIα or -β, is up regulated in aged and denervated soleus muscle and that CaMKIV is absent in skeletal but not cardiac muscle. Whether CaMKIIγ up-regulation is part of the pathology of wasting or a result of some adaptational response to atrophy is not known. Future studies will be important in determining whether insights from the adaptational response of muscle to increased loads will provide pharmacological approaches for increasing muscle strength or endurance to counter muscle wasting.

Increasing awareness of hazards associated with the use of antibiotic and chemical feed additives has accelerated investigations into plants and their extracts as feed additives. The present review mainly discusses two classes of plant secondary compounds in this context, i.e. essential oils and saponins. The broader potential of plants and their extracts is illustrated by the progress of an EC Framework 5 project, ‘Rumen-up’. Dietary inclusion of a commercial blend of essential oils causes markedly decreased NH3 production from amino acids in rumen fluid taken from sheep and cattle. This effect is mediated partly by the effects on hyper-NH3-producing bacteria and the protein- and starch-fermenting rumen bacterium, Ruminobacter amylophilus. Saponin-containing plants and their extracts suppress the bacteriolytic activity of rumen ciliate protozoa and thereby enhance total microbial protein flow from the rumen. The effects of some saponins are transient, because saponins are hydrolysed by bacteria to their corresponding sapogenin aglycones, which are much less toxic to protozoa. Saponins also have selective antibacterial effects that may prove useful in, for example, controlling starch digestion. The ‘Rumen-up’ project began with a targetted collection of European plants and their extracts, which partners have tested for their effects on rumen proteolysis, protozoa, methanogenesis and lactate production. A success rate of about 5% in terms of positive hits illustrates that plant secondary compounds, of which essential oils and saponins comprise a small proportion, have great potential as ‘natural’ manipulators of rumen fermentation to benefit the farmer and the environment in the future.

Differences in whole-body lipid metabolism between men and women are indicated by lower-body fat accumulation in women but more marked accumulation of fat in the intra-abdominal visceral fat depots of men. Circulating blood lipid concentrations also show gender-related differences. These differences are most marked in premenopausal women, in whom total cholesterol, LDL-cholesterol and triacylglycerol concentrations are lower and HDL-cholesterol concentration is higher than in men. Tendency to accumulate body fat in intra-abdominal fat stores is linked to increased risk of CVD, metabolic syndrome, diabetes and other insulin-resistant states. Differential regional regulation of adipose tissue lipolysis and lipogenesis must underlie gender-related differences in the tendency to accumulate fat in specific fat depots. However, empirical data to support current hypotheses remain limited at the present time because of the demanding and specialist nature of the methods used to study adipose tissue metabolism in human subjects. In vitro and in vivo data show greater lipolytic sensitivity of abdominal subcutaneous fat and lesser lipolytic sensitivity of femoral and gluteal subcutaneous fat in women than in men. These differences appear to be due to fewer inhibitory α adrenergic receptors in abdominal regions and greater α adrenergic receptors in gluteal and femoral regions in women than in men. There do not appear to be major gender-related differences in rates of fatty acid uptake (lipogenesis) in different subcutaneous adipose tissue regions. In visceral fat rates of both lipolysis and lipogenesis appear to be greater in men than in women; higher rates of lipolysis may be due to fewer α adrenergic receptors in this fat depot in men. Fatty acid uptake into this depot in the postprandial period is approximately 7-fold higher in men than in women. Triacylglycerol concentrations appear to be a stronger cardiovascular risk factor in women than in men, with particular implications for cardiovascular risk in diabetic women. The increased triacylglycerol concentrations observed in women taking hormone-replacement therapy (HRT) may explain the paradoxical findings of increased rates of CVD in women taking HRT that have been reported from recent primary and secondary prevention trials of HRT.

The physiological function of the mitochondrial uncoupling protein (UCP), UCP3, is still under debate. There is, however, ample evidence to indicate that, in contrast to UCP1, the primary function of UCP3 is not the dissipation of energy. Rather, several lines of evidence suggest that UCP3 is associated with cellular fatty acid metabolism. The highest levels of expression of UCP3 have been found in type 2 glycolytic muscle fibres, and fasting and high-fat diets up regulate UCP3. This up-regulation is most pronounced in muscle with a low fat oxidative capacity. Acute exercise also up regulates UCP3, and this effect has been shown to be a result of the exercise-induced increase in plasma fatty acid levels. In contrast, regular physical activity, which increases fat oxidative capacity, reduces UCP3 content. Based on these data it has been postulated that UCP3 functions to export those fatty acids that cannot be oxidized from the mitochondrial matrix, in order to prevent fatty acid accumulation inside the matrix. Several experiments have been conducted to test this hypothesis. Blocking carnitine palmitoyltransferase 1, thereby reducing fat oxidative capacity, rapidly induces UCP3. High-fat diets, which increase the mitochondrial supply of fatty acids, also up regulate UCP. However, feeding a similar amount of medium-chain fatty acids, which can be oxidized inside the mitochondrial matrix and therefore does not need to be exported from the matrix, does not affect UCP3 protein levels. In addition, UCP3 is increased in patients with defective β-oxidation and is reduced after restoring oxidative capacity. In conclusion, it is suggested that UCP3 has an important physiological function in facilitating outward transport from the mitochondrial matrix of fatty acid anions that cannot be oxidized, thereby protecting against lipid-induced mitochondrial damage.

The purported antiparasitic properties of plant secondary metabolites (PSM) have been the cause of controversy amongst the scientific community. Despite long-standing knowledge of the prophylactic and therapeutic properties of PSM-rich extracts, which comes mainly from ethnoveterinary sources, the scientific evidence of the antiparasitic effects of PSM is inconsistent. In the first part of the present paper the causes of this controversy are addressed, and the evidence available on the antiparasitic effects of PSM is critically examined. The focus is on examples of the antiparasitic activity of PSM against helminth nematodes. The conclusion is that PSM can have antiparasitic properties, which depend on their structure, level of ingestion and availability within the gastrointestinal tract of the animal. The second part is an appraisal of the potential role of PSM for parasite control in ruminant production systems. Despite their antiparasitic properties, PSM consumption does not necessarily have positive consequences in parasitised herbivores, as excessive consumption of PSM can adversely affect herbivore fitness and survival, through their anti-nutritional properties. For this reason it is suggested that the antiparasitic properties of PSM should be assessed at the same time as their anti-nutritional effects. The same measure, e.g. the performance of parasitised hosts, should be used when assessing these properties. The assessment of the costs and benefits suggests that parasitised herbivores can benefit from the long-term consumption of PSM only if the antiparasitic benefits outweigh the anti-nutritional costs of PSM. In addition, it is proposed that parasitised animals might be able to benefit from PSM consumption even if their performance is impaired, as long as the latter is a short-term compromise that leads to long-term benefits.

The protein import process of mitochondria is vital for the assembly of the hundreds of nuclear-derived proteins into an expanding organelle reticulum. Most of our knowledge of this complex multisubunit network comes from studies of yeast and fungal systems, with little information known about the protein import process in mammalian cells, particularly skeletal muscle. However, growing evidence indicates that the protein import machinery can respond to changes in the energy status of the cell. In particular, contractile activity, a powerful inducer of mitochondrial biogenesis, has been shown to alter the stoichiometry of the protein import apparatus via changes in several protein import machinery components. These adaptations include the induction of cytosolic molecular chaperones that transport precursors to the matrix, the up-regulation of outer membrane import receptors, and the increase in matrix chaperonins that facilitate the import and proper folding of the protein for subsequent compartmentation in the matrix or inner membrane. The physiological importance of these changes is an increased capacity for import into the organelle at any given precursor concentration. Defects in the protein import machinery components have been associated with mitochondrial disorders. Thus, contractile activity may serve as a possible mechanism for up-regulation of mitochondrial protein import and compensation for mitochondrial phenotype alterations observed in diseased muscle.

The present paper provides an overview of the methodological principles that underpinqualitative research and how these principles differ from those of quantitative research. It is intended to set the scene for the following papers that outline two specific approaches to the analysis of qualitative data. Within the tradition of qualitative research there are many different theoretical perspectives, of which these approaches are only two examples, but they need to be set within this broader tradition in order to highlight their specific features. Qualitative and quantitative research differ from each other in far more than their methods and data. They are each based on very different premises about both the nature of the world and the nature of our knowledge of it and how this information is generated. These approaches have implications for all aspects of research strategy, including the assessment of the quality of research findings and their wider utility or application. In relation to the latter, lack of detail in the reporting of qualitative research and small sample sizes has tended to create the impression that the findings of qualitative research have little application outside the particular research setting. While there is need for more rigor in reporting, it needs to be recognized that qualitative research can offer insights and understandings with wider relevance, althoughthese outcomes are of a different type from those provided by quantitative research.

Issues arising in connection with genes and nutrition policy include both nutrigenomics and nutrigenetics. Nutrigenomics considers the relationship between specifc nutrients or diet and gene expression and, it is envisaged, will facilitate prevention of diet-related common diseases. Nutrigenetics is concerned with the effects of individual genetic variation (single nucleotide polymorphisms) on response to diet, and in the longer term may lead to personalised dietary recommendations. It is important also to consider the surrounding context of other issues such as novel and functional foods in so far as they are related to genetic modification. Ethical issues fall into a number of categories: (1) why nutrigenomics? Will it have important public health benefits? (2) questions about research, e.g. concerning the acquisition of information about individual genetic variation; (3) questions about who has access to this information, and its possible misuse; (4) the applications of this information in terms of public health policy, and the negotiation of the potential tension between the interests of the individual in relation to, for example, prevention of conditions such as obesity and allergy; (5) the appropriate ethical approach to the issues, e.g. the moral difference, if any, between therapy and enhancement in relation to individualised diets; whether the 'technological fix' is always appropriate, especially in the wider context of the purported lack of public confidence in science, which has special resonance in the sphere of nutrition.

The present paper introduces interpretative phenomenological analysis (IPA) as a framework for analysing qualitative research data collected for public health nutrition and dietetic research studies. The theoretical roots of IPA have been set out briefly in order to help researchers decide whether the approach is relevant for them and their particular research questions. IPA can be used to analyse data from one-to-one interviews in order to develop ‘thick descriptions’ that may help illuminate human experience. IPA can also be used to develop theories and/or models, which could help inform policy. The main body of the paper describes the analytical techniques and procedures used to achieve both outcomes in a practical way, using examples from the author's own research. In the following paper Krueger's methods for analysing focus group data are set out for comparison. It is hoped that these papers will empower researchers with little experience of qualitative research to develop confidence with qualitative data analysis. In addition, it is hoped that the material will stimulate debate amongst more experienced qualitative researchers from a public health or dietetic background.

Is the information currently available to adjust nutritional recommendations and develop individualized nutrition? No. There is not even the information needed for setting dietary recommendations with confidence now at the group level. Will it be available soon? The answer to this question depends on the drive and will of the nutritional community, the success in recruiting funding to the area, the education of nutritionists and the spawning of great ideas and approaches. The emerging tools of genomics, proteomics and metabolomics are enabling the in-depth study of relationships between diet, genetics and metabolism. The advent of technologies can be compared with the discovery of the microscope and the new dimensions of scientific visualization enabled by that discovery. Nutritionists stand at the crest of new waves of data that can be generated, and new methods for their digestion will be required. To date, the study of dietary requirements has been based largely on a black box approach. Subjects are supplemented or depleted and clinical outcomes are observed. Few recommendations are based on metabolic outcomes. Metabolomics and nutrigenomics promise tools with which recommendations can be refined to meet individual requirements and the potential of individualized nutrition can be explored. As yet, these tools are not being widely applied in nutritional research and are rarely being applied by nutritionists. The result is often interesting research that is frequently nutritionally flawed, resulting in inappropriate conclusions. Nutritional education is needed to put nutritionists at the forefront of the development of applications for these technologies, creating a generation of nutrigenomicists. A new generation of nutritionists should be working interdisciplinarily with geneticists, molecular biologists and bioinformaticians in the development of research strategies. The present paper reviews the current status of nutrigenomic research, the current controversies and limitations, and developments needed to advance nutrigenomics and explore fully the promise of individualized nutritional recommendations.

The role of intramyocellular triacylglycerol (IMTG) as a substrate source during exercise has recently regained much attention as a result of the proposed functional relationship between IMTG accumulation and the development of insulin resistance. It has been speculated that elevated NEFA delivery and/or impaired fatty acid (FA) oxidation result in intramyocellular accumulation of triacylglycerol and FA metabolites, which are likely to induce defects in the insulin signalling cascade, causing insulin resistance. The progressive accumulation of IMTG in sedentary patients and patients who are obese and/or have type 2 diabetes should therefore form a major therapeutic target, and efforts should be made to develop interventions that prevent excess IMTG accretion by stimulating their rate of oxidation. Although regular exercise is likely to represent such an effective means, there is much controversy about the actual contribution of the IMTG pool as a substrate source during exercise. The apparent discrepancy in the published literature might be explained by differences in the applied research protocol and the selected subject population, but most of all by the techniques that have been employed to estimate IMTG use during exercise. Data obtained in trained-endurance athletes indicate that athletes can substantially reduce their IMTG pool following a single exercise session. With the growing awareness that skeletal muscle has a tremendous potential to oxidise IMTG during prolonged moderate-intensity exercise, more research is warranted to develop combined exercise, nutritional and/or pharmacological interventions that can stimulate IMTG oxidation in sedentary patients and patients who are obese and/or have type 2 diabetes.

Intramyocellular triacylglycerol (TG) is an important energy store, and the energy content of this depot is higher than the energy content of the muscle glycogen depot. It has recently been shown that the mobilization of fatty acids from this TG pool may be regulated by the neutral lipase hormone-sensitive lipase (HSL). This enzyme is known to be rate limiting for intracellular TG hydrolysis in adipose tissue. The presence of HSL has been demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative fibres than in glycolytic fibres. When analysed under conditions optimal for“ HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by the presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via β-adrenergic activation of cAMP-dependent protein kinase (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser563, Ser659and Ser660. Contraction probably also enhances muscle HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is elevated by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal-regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle the activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser600. Hence, phosphorylation of different sites may explain the finding that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases contraction-mediated HSL activation but diminishes adrenaline-mediated HSL activation in muscle. In conclusion, HSL is present in skeletal muscle and can be activated by phosphorylation in response to both adrenaline and muscle contractions. Training increases contraction-mediated HSL activation, but decreases adrenaline-mediated HSL activation in muscle.

The unravelling of the human genome has the potential to radically extend many of the strategies used in public health nutrition to improve health and to increase food availability, accessibility and utilization. The present paper divides nutrigenomics into two broad but differing areas in asking about possible public health applications: (1) the increasing mismatch between population growth and global food security, on top of the already approximately 800 million of the world population who are food insecure; (2) possible responses to the rising prevalence of non-communicable diseases as the Western diet becomes increasingly inappropriate to the needs of those consuming it. It is clear that complex interactions of multiple polymorphisms play a role in how individuals and sub-populations respond to dietary interventions. All these applications present public health and ethical challenges, particularly in ensuring that any benefits that do come from nutrigenomics are not restricted to the wealthy minority of only the affluent nations. The present paper concludes that the public health applications of nutrigenomics are probably at least a decade away, especially for developing countries. Clinical applications are likely to be more immediate, probably resulting in ‘designer diets’ for individuals with particular polymorphisms, but unless governments take on the role of ensuring some extent of equity in access, any benefits are most likely to go to those who can afford the screening, tests and treatment. At the same time, greatly increased international efforts are needed towards the continuing, and in some cases worsening, global malnutrition, as genetic manipulation of crops is unlikely to provide more than part of the solution.

In recent years focus-group interviews, as a means of qualitative data collection, have gained popularity amongst professionals within the health and social care arena. Despite this popularity, analysing qualitative data, particularly focus-group interviews, poses a challenge to most practitioner researchers. The present paper responds to the needs expressed by public health nutritionists, community dietitians and health development specialists following two training sessions organised collaboratively by the Health Development Agency, the Nutrition Society and the British Dietetic Association in 2003. The focus of the present paper is on the concepts and application of framework analysis, especially the use of Krueger's framework. It provides some practical steps for the analysis of individual data, as well as focus-group data using examples from the author's own research, in such a way as to assist the newcomer to qualitative research to engage with the methodology. Thus, it complements the papers by Draper (2004) and Fade (2004) that discuss in detail the complementary role of qualitative data in researching human behaviours, feelings and attitudes. Draper (2004) has provided theoretical and philosophical bases for qualitative data analysis. Fade (2004) has described interpretative phenomenology analysis as a method of analysing individual interview data. The present paper, using framework analysis concentrating on focus-group interviews, provides another approach to qualitative data analysis.

Hormone-sensitive lipase (HSL) is believed to play a regulatory role in initiating the degradation of intramuscular triacylglycerol (IMTG) in skeletal muscle. A series of studies designed to characterise the response of HSL to three stimuli: exercise of varying intensities and durations; adrenaline infusions; altered fuel supply have recently been conducted in human skeletal muscle. In an attempt to understand the regulation of HSL activity the changes in the putative intramuscular and hormonal regulators of the enzyme have also been measured. In human skeletal muscle at rest there is a high constitutive level of HSL activity, which is not a function of biopsy freezing. The combination of low adrenaline and Ca2+levels and resting levels of insulin appear to dictate the level of HSL activity at rest. During the initial minute of low and moderate aerobic exercise HSL is activated by contractions in the apparent absence of increases in circulating adrenaline. During intense aerobic exercise, adrenaline may contribute to the early activation of HSL. The contraction-induced activation may be related to increased Ca2+and/or other unknown intramuscular activators. As low- and moderate-intensity exercise continues beyond a few minutes, activation by adrenaline through the cAMP cascade may also occur. With prolonged moderate-intensity exercise beyond 1–2 h and sustained high-intensity exercise, HSL activity decreases despite continuing increases in adrenaline, possibly as a result of increasing accumulations of free AMP, activation of AMP kinase and phosphorylation of inhibitory sites on HSL. The existing work in human skeletal muscle also suggests that there are numerous levels of control involved in the regulation of IMTG degradation, with control points downstream from HSL also being important. For example, it must be remembered that the actual flux (IMTG degradation) through HSL may be allosterically inhibited during prolonged exercise as a result of the accumulation of long-chain fatty acyl-CoA.

The present article addresses the hypothesis that disturbances in skeletal muscle fatty acid handling in abdominal obesity and type 2 diabetes mellitus may play a role in the aetiology of increased adipose tissue stores, increased triacylglycerol storage in skeletal muscle and skeletal muscle insulin resistance. The uptake and/or oxidation of fatty acids have been shown to be impaired during post-absorptive conditions in abdominally-obese subjects and/or subjects with type 2 diabetes. Also, human studies have shown that muscle of subjects that are (abdominally) obese and/or have type 2 diabetes is characterized by an inability to increase fatty acid uptake and/or fatty acid oxidation during β-adrenergic stimulation and exercise. This disturbance in fat oxidation may promote, on one hand, the development of increased adipose tissue stores and obesity. On the other hand, fatty acids that are taken up by muscle and not oxidized may increase triacylglycerol storage in muscle, which has been associated with skeletal-muscle insulin resistance. Disturbances in the capacity to increase fat oxidation during post-absorptive conditions, β-adrenergic stimulation and exercise in subjects who are obese and/or have type 2 diabetes persist after weight reduction, indicating that the diminished fat oxidation may be a primary factor leading to the obese and/or insulin-resistant state rather than an adaptational response. Clearly, the precise sequence of events leading to an increased adiposity and insulin resistance in obesity and type 2 diabetes mellitus is not yet fully understood.

Repeated bouts of resistance exercise produce an increase in skeletal muscle mass. The accumulation of protein associated with the growth process results from a net increase in protein synthesis relative to breakdown. While the effect of resistance exercise on muscle mass has long been recognized, the mechanisms underlying the link between high-resistance contractions and the regulation of protein synthesis and breakdown are, to date, poorly understood. In the present paper skeletal muscle will be viewed as a mechanosensitive cell type and the possible mechanisms through which mechanically-induced signalling events lead to changes in rates of protein synthesis will be examined.

Insulin-like growth factor 1 (IGF-1) has been shown to rescue the aging-related or inactivity-induced loss of muscle mass through the activation of satellite cells. However, the signalling pathways and the mechanism by which IGF-1 affects satellite cells have not been not completely identified. The purpose of the present review is to provide current understanding of the cellular and molecular events underlying IGF-1 induced proliferation of satellite cells.