Re´sume´

Jusqu'il y a 15 ou 20 ans, des nombreux nutritionnistes étaient intéressés principalement dans les effets de l'alimentation sur des paramètres de santé comme la pression sanguine et les concentrations de cholestérol dans le sérum. Ces études ont signifié sans doute une contribution très important à la compréhension actuelle de la relation entre l'alimentation et la santé. Cependant, et pour de nombreuses raisons, il n'y a pas eu beaucoup de monde qui a essayé d'expliquer ces effets au niveau moléculaire. Toutefois, il paraîtra qu'aujourd'hui la tendance a était renversé; un grand nombre de travaux de recherche sont dédié a l'exploration des effets des components de l'alimentation à niveau moléculaire. Ce type de recherche a était fait possible grâce, entre autres facteurs, à l'implémentation de techniques des sciences plus fundamentaux à la recherche dans la nutrition. Ce aussi la disponibilité des séquences du génome qui a accéléré ce changement d'intéret. Les objectives de ce projet sont l'obtention d'une information précis sur les réponses métaboliques et moléculaires des cellules et des tissues (ou même de l'organisme entier) aux components diététiques. Dans ces études, les interactions entre l'alimentation et l'héritage génétique, ainsi qu'entre l'alimentation et des conditions physiologiques et psychologiques doivent aussi etre adressées. Cependant, il n'est pas seulement important l'obtention d'information sur les mécanismes, mais aussi sur les conséquences fonctionnelles pour l'organisme. Une dernière question se pose sur l'usage de cette information pour le développement de tests capable de prescrire des conseils diététiques aux subpopulations spécifiques. Ces questions stimulantes peuvent juste etre abordées à travers d'une approximation intégrée combinant l'expertise de plusieurs disciplines.

Nutritional strategies for optimising bone health throughout the life cycle are extremely important, since a dietary approach is more popular amongst osteoporosis sufferers than drug intervention, and long-term drug treatment compliance is relatively poor. As an exogenous factor, nutrition is amenable to change and has relevant public health implications. With the growing increase in life expectancy, hip fractures are predicted to rise dramatically in the next decade, and hence there is an urgent need for the implementation of public health strategies to target prevention of poor skeletal health on a population-wide basis. The role that the skeleton plays in acid-base homeostasis has been gaining increasing prominence in the literature; with theoretical considerations of the role alkaline bone mineral may play in the defence against acidosis dating as far back as the late 19th century. Natural, pathological and experimental states of acid loading and/or acidosis have been associated with hypercalciuria and negative Ca balance and, more recently, the detrimental effects of ‘acid’ from the diet on bone mineral have been demonstrated. At the cellular level, a reduction in extracellular pH has been shown to have a direct enhancement on osteoclastic activity, with the result of increased resorption pit formation in bone. A number of observational, experimental, clinical and intervention studies over the last decade have suggested a positive link between fruit and vegetable consumption and the skeleton. Further research is required, particularly with regard to the influence of dietary manipulation using alkali-forming foods on fracture prevention. Should the findings prove conclusive, a “fruit and vegetable” approach to bone health maintenance may provide a very sensible (and natural) alternative therapy for osteoporosis treatment, which is likely to have numerous additional health-related benefits.

Undernutrition is commonly associated with chronic disease in children and the elderly. Overnutrition is also, but less commonly, associated with chronic illness. In most diseases malnutrition arises because energy intake does not match energy output. Traditionally, the focus of research has been on abnormalities in energy expenditure, in the belief that these factors were the main determinants of energy imbalance. Recent studies using the doubly-labelled-water method to measure total energy expenditure, combined with more complex study design, have suggested an alternative conclusion. In many chronic diseases patient behaviour, and particularly energy intake, is responsible for energy imbalance and malnutrition. Energy balance studies have therefore provided a useful foundation for the design of strategies aimed at preventing or managing chronic malnutrition. However, modifying patient behaviour is an ambitious undertaking which may not be within the scope of existing clinical nutrition services. A number of non-traditional models of managing chronic malnutrition in children and the elderly are promising. Increasing recognition of the value of systematic review will also provide improved strategies for prevention and management of chronic malnutrition.

Insulin resistance develops as a response to virtually all types of surgical stress. There is an increasing body of evidence that suggests that insulin resistance in surgical stress is not beneficial for outcome. A recent large study in intensive-care patients showed that aggressive treatment of insulin resistance using intravenous insulin reduced mortality and morbidity substantially. Similarly, in burn patients, intensive insulin and glucose treatment has been shown to improve N economy and enhance skin-graft healing. In surgical patients insulin resistance has been characterized in some detail, and has been shown to have many similarities with metabolic changes seen in patients with type 2 diabetes. This finding may be important since insulin resistance has been shown to be one independent factor that influences length of stay. When patients about to undergo elective surgery have been treated with glucose intravenously or a carbohydrate-rich drink instead of overnight fasting, insulin resistance was reduced by about half. A small meta-analysis showed that when post-operative insulin resistance was reduced by preoperative carbohydrates, length of hospital stay was shortened. Overnight intravenous glucose at high doses improved post-operative N economy. This type of treatment has also been shown repeatedly to reduce cardiac complications after open-heart surgery. Furthermore, if the carbohydrates are given as a drink pre-operatively, pre-operative thirst, hunger and anxiety are markedly reduced. In summary, preventing or treating insulin resistance in surgical stress influences outcome. Fasting overnight is not an optimal way to prepare patients for elective surgery. Instead, pre-operative carbohydrates have clinical benefits.

Aging is a complex biological process, which usually is accompanied by changes in socioeconomic status, which may have a great impact on the physical and nutritional status of the elderly. Decreased food intake and a sedentary lifestyle in the growing numbers of the elderly increase their risk for malnutrition, decline of bodily functions and developing chronic diseases. Oxidative stress is believed to be an important factor in aging and many age-associated degenerative diseases. Modulation of oxidative stress by energy restriction in animals has been shown to be one of the mechanisms for retarding the aging process. Dietary antioxidants are regarded as being important in modulating oxidative stress of aging and age-associated diseases. Supplementation of the elderly with vitamin E has been shown to enhance immune response, delay onset of Alzheimer's disease, and increase resistance to oxidative injury associated with exercise. Vitamin E, in comparison with other antioxidants, is also effective in reducing viral titres, but not the longevity of middle-aged mice. Our studies have indicated that polyphenols or vitamin E may assist in preventing cardiovascular disease, in part by decreasing expression by endothelial cells of proinflammatory cytokines, adhesion molecules, and monocyte adhesion. Most recently, we have found that some of these antioxidants may prevent tumour growth by inhibiting angiogenesis via suppression of interleukin 8 and modulation of the cell junction molecule, VE-cadherin. These findings provide further support for the consumption of fruit and vegetables, which contain several forms of phytochemicals with antioxidant activity, in order to reduce the risk of cardiovascular disease and cancer, the leading causes of morbidity and mortality among the elderly.

In the present paper the prevalence of obesity (BMI 30 kg/m2) and current physical activity levels in Irish adults have been evaluated. The prevalence of obesity in Irish adults is currently 18 %, with men at 20 % and women at 16 %. A further 47 % of men and 33 % of women are overweight (BMI 25·0–29·9 kg/m2). Since 1990, obesity has more than doubled in men from 8 % to 20 %, and increased from 13 % to 16 % in women. The highest prevalence of obesity (30 %) was found in women aged 51–64 years. Defined waist circumference action levels identified 48 % of the population who are in need of weight management and who also are at a 1·5–4·5 times increased risk of having at least one cardiovascular disease risk factor. Physical activity levels were low overall. Men were more active in work and recreational pursuits than women, but women were more active in household activities. Walking was the most popular recreational pursuit. However, TV viewing occupied most of the leisure time of men and women. Higher levels of activity were associated with a lower BMI and waist circumference. The results indicate the need for sensitive and individualised strategies to promote physical activity and to achieve a healthy weight status.

Résumé

La distribution intracellulaire des micronutriments ainsi que leur absorption sont importantes pour les fonctions cellulaires. Dans certains cas la distribution des micronutriments ou des protéines associées est déterminée par des mécanismes liés à l'expression des gènes. La région 3' non traduite (3'UTR) de l'ARNm de la métallothioneine-1 détermine la localisation de ce message et, par conséquent, la localisation intracellulaire de la protéine qu'il code. En utilisant des cellules transfectées nous avons montré que la métallothioneine-1 est transportée vers le noyau ou elle exerce un rôle dans la protection contre le stress oxydant et les dommages causés à l'ADN. Quand l'apport nutritionnel en Se est limité, l'expression des sélénoproteines est altérée. Toutefois celle-ci n'est pas affectée de fac¸on identique pour toutes les sélénoproteines; le Se disponible étant utilisé de fac¸on prioritaire pour la synthèse de certaines d'entre elles. Cet ordre de priorité met en jeu des différences dans la traduction et la stabilité de leur ARNm qui sont sous le controle de séquences dans la région 3' non traduite. Potentiellement, des variations génétiques affectant ces mécanismes régulateurs peuvent moduler les besoins en nutriments. Des polymorphismes génétiques ont été décrits dans le 3'UTR des ARNm de deux sélénoproteines; l'un d'entre eux affectant la synthèse de la sélénoproteine correspondante. Ces exemples illustrent comment des approches moléculaires peuvent contribuer à accroître notre compréhension du métabolisme et des besoins en nutriments à différents niveaux. Premièrement, elles permettent d'étudier les effets régulateurs des gènes et de leurs produits. Ensuite, la compréhension de ces effets peut fournir un modèle pour étudier le métabolisme des nutriments au niveau cellulaire. Ainsi, lorsque des effets essentiels sont identifiés, la connaissance du génome humain et les bases de données sur les polymorphismes génétiques constituent des outils complémentaires pour définir l'étendue de la variation génétique des gènes revêtant une importance nutritionnelle. Enfin, la fonctionnalité de ces variations peut être définie et des sous-groupes de la population, possédant des besoins nutritionnels différents, peuvent etre identifiés.

Osteoporosis is a common disease in the elderly, and the fractures that result from this disorder affect 40 % of women and 14 % of men over the age of 50 years. The risk of fracture relates to bone mineral density and the risk of falling, among other factors. Low bone mineral density in the elderly can result from either low peak bone mass or accelerated bone loss, or a combination of the two. Nutritional factors play a role in both the attainment of peak bone mass and in the rate of age-related bone loss. The main determinants of peak bone mass are genetic factors, early-life nutrition, diet and exercise. Of the nutritional factors Ca, and particularly milk, are the most important contributors to peak bone mass. Some of these factors may interact; for example, a low dietary Ca in addition to an unfavourable vitamin D receptor gene polymorphism may result in low peak bone mass. The age-related changes in bone mass may also have a genetic basis, but deficiency of oestrogen is a major contributor. In addition, undernutrition is common in the elderly, and lack of dietary protein contributes both to impaired bone mineral conservation and increased propensity to fall. There is a decreased ability of the intestine to adapt to a low-Ca diet with increasing age. Other dietary factors include vitamin K, Zn and fruit and vegetables. Adequate nutritional status, particularly of Ca and vitamin D, is essential for the successful pharmaceutical treatment of osteoporosis. Thus, strategies for enhancing skeletal health in the elderly must begin in early childhood, and continue throughout life.

General anaesthesia causes hypothermia due to decreased metabolic rate and impaired thermoregulation. Many warming devices are in use to prevent heat loss, but little attention has been paid to stimulating the body's own heat generation. All nutrients raise energy expenditure, and the highest thermic effect is ascribed to amino acids and proteins, 30–40% in the awake state. Amino acids infused during general anaesthesia exert a thermic effect that is enhanced compared with that in the awake state. At awakening from anaesthesia, post-operative hypothermia may be prevented without shivering. The tissues involved and the mechanisms by which nutrients stimulate heat production are still not completely understood. However, these findings support the existence of an inhibitory action normally exerted by central thermosensors, in order to maintain oxidative metabolism within certain limits, to prevent hyperthermia. During anaesthesia central thermosensors are silenced and, hence, amino acid thermogenesis is exaggerated. The amino acid-induced heat generation during anaesthesia predominantly occurs in extra-splanchnic tissues, most probably in skeletal muscle. It may reflect an increased protein turnover, as both protein breakdown and synthesis are energy-consuming processes known to generate heat. Possibly, amino acid infusion provides substrates, otherwise mobilized from the body's own tissues, needed for wound healing and immunological function. However, other cellular mechanisms may also contribute to this non-shivering thermogenesis.

The high incidence of obesity in Ireland is of growing concern. The Irish Universities Nutrition Alliance North/South Food Consumption Survey found that 18 % of the population are obese and 39 % overweight. Obesity and overweight increase the risk of developing CHD, type 2 diabetes, hypertension and some forms of cancer. It is well accepted that the best treatment for obesity is a combination of energy intake reduction and regular exercise. Previously, dietary compliance has been shown to improve when monitored on a regular basis. The lengthy delay between clinic visits to the dietitian has been reported by those who failed to lose weight to be the main reason for poor compliance. A weight monitoring clinic was designed to offer those requiring regular support and encouragement the opportunity to monitor their weights on a more regular basis, while waiting for their return visit to the dietitian in the Outpatient Departments. As resources were limited, an efficient use of time was essential. The clinic design was: 1 h/week; eight to fourteen appointments per clinic; weekly or fortnightly visit; return patients only. The clinic was started on a trial basis in June 1999, and was evaluated in December 2000. Referrals were only taken from other dietitians, and each participant was informed in advance of the necessity of having a return Outpatient Department appointment for full dietary review. Forty-eight participants attended more than three times up to and including December 2000 (seven males, forty-one females). The number of clinic visits ranged from three to twenty-eight. Mean weight at start of clinic was 92·94 kg. Of the group attending, 67 % (thirty-two) successfully lost weight and maintained this weight loss. This ranged from 0·1 kg to 23·5 kg. While in total 31 % (fifteen) of attendees had gained weight at December 2000, all attendees, including this fifteen, had lost weight at some point during the clinic. Self-reported reasons given for weight regain included: (1) non-attendance at weight clinic (40 %); (2) Christmas or holidays (13 %); (3) stress related to family, work (13 %); (4) ill-health or medication (13 %). The remaining 20 % reported no reason. Other findings included better compliance with diet and improved overall balance. There was an overall improvement in other dietary-related problems, e.g. reduced cholesterol, improved glycaemic control, reduced blood pressure. The participants attending the clinic reported decreased clothes size and improved self-image and confidence. They were more enthusiastic about dietary compliance, and all attendees expressed their satisfaction with the clinic and the service.

Résumé

La vitamine E, l'antioxydant liposoluble le plus important, fut découverte à l'Université de Californie à Berkeley en 1922. Depuis sa découverte, les études sur les tocophérols et les tocotrienols que constitue cette vitamine, ont été centrées pour la plupart sur leurs propriétés antioxydantes. En 1991, le groupe de Angelo Azzi (Boscoboinik et al. 1991a,b) fut le premier à décrire les fonctions autres que les antioxydantes et de transmission de signaux de l'α-tocophérol, en démontrant la régulation par la vitamine E de l'activité de la protéine kinase C dans les cellules de muscle lisse. Au niveau de la transcription, l'²-tocophérol module l'expression de la protéine de transfert hépatique de l'α-tocophérol, ainsi que l'expression du ge`ne alpha1 du collage`ne du foie, du ge`ne de la collagénase et du ge`ne de l'α-tropomyosine. Récemment, un facteur de transcription dépendant du tocophérol (la protéine associée au tocophérol) a été découvert. Il a été démontré sur des cellules cultivées que la vitamine E inhibe l'inflammation, l'adhésion cellulaire, l'agrégation des plaquettes et la prolifération des cellules de muscle lisse. Les avancées récentes de la biologie moléculaire et des techniques génomiques ont conduit à la découverte de nouveaux ge`nes et des mécanismes de transduction des signaux sensibles à la vitamine E.

The n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoicacid (DHA) are found in high proportions in oily fish and fish oils. The n-3 PUFA are structurally and functionally distinct from the n-6 PUFA. Typically, human inflammatory cells contain high proportions of the n-6 PUFA arachidonic acid and low proportions of n-3 PUFA. The significance of this difference is that arachidonic acid is the precursor of 2-series prostaglandins and 4-series leukotrienes, which are highly-active mediators of inflammation. Feeding fish oil results in partial replacement of arachidonic acid in inflammatory cell membranes by EPA. This change leads to decreased production of arachidonic acid-derived mediators. This response alone is a potentially beneficial anti-inflammatory effect of n-3 PUFA. However, n-3 PUFA have a number of other effects which might occur downstream of altered eicosanoid production or might be independent of this activity. For example, animal and human studies have shown that dietary fish oil results in suppressed production of pro-inflammatory cytokines and can decrease adhesion molecule expression. These effects occur at the level of altered gene expression. This action might come about through antagonism of the effects of arachidonic acid-derived mediators or through more direct actions on the intracellular signalling pathways which lead to activation of transcription factors such as nuclear factor kappa B (NFêB). Recent studies have shown that n-3 PUFA can down regulate the activity of the nuclear transcription factor NFêB. Fish oil feeding has been shown to ameliorate the symptoms in some animal models of chronic inflammatory disease and to protect against the effects of endotoxin and similar inflammatory challenges. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are antiinflammatory. There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.

Résumé

Alors que l'alimentation de l'homme a beaucoup évoluée depuis ses origines, le génome humain est resté très stable. Pourtant, de très nombreux gènes ont des polymorphismes connus. En fait, on considère maintenant que les principales pathologies humaines (maladies cardiovasculaires, diabète, obésité et cancers) résultent d'une interaction entre des facteurs de succeptibilité génétique et des facteurs de l'environement, dont l'alimentation. Dans le domaine du métabolisme des lipoprotéines et des maladies cardiovasculaires, des polymorphimes de plusieurs gènes ont été identifiés et associés aux niveaux des paramètres lipidiques ou aà des réponses variables aux régimes, comme pour les apoprotéines (apo) E, B, A-IV et C-III, le LDL récepteur, la protéine microsomiale de transport (MTP), la protéine de liason des acides gras (FABP), la protéine de transport des esters de cholésterol (CETP), la lipoprotéine lipase ou la lipase hepatique. Nous réalisons une étude d'intervention à Marseille dans le but d'étudier l'interaction