Symposium on ‘Functionality of nutrients and behaviour’
Food choice and intake: the human factor
- David J. Mela
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- 28 February 2007, pp. 513-521
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Human perceptions and selection of food are derived from the prevailing and momentary food, agro-economic and cultural environment, cognitive and biological characteristics of individuals, and the real and perceived intrinsic and extrinsic attributes of foods themselves. The range of items typically chosen and consumed within a given population is largely determined by interaction of the external environmental context with guiding sets of implicit and explicit social and psychobiological ‘rules’. Within the rather broad limits of biology, individual food choices and intake behaviours relate to and reflect aspects of food availability, existing habitual behaviours, learning mechanisms, and individual beliefs and expectations. Many of the relevant features of these variables are uniquely human, together determining what is ‘food’, when, how, by and with whom it is chosen and eaten, and in what quantities. They also provide the opportunities for individuals to establish and maintain a relatively stable set of culturally and biologically determined affective responses (‘likes’) and intake behaviours. Understanding of the potential contribution of these influences under different conditions can serve to explain many of the observed characteristics of human eating, and highlight potential avenues for intervention.
The effect of nutrients on feed intake in ruminants
- P. Faverdin
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- Published online by Cambridge University Press:
- 28 February 2007, pp. 523-531
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The purpose of the present review is to examine the role played by nutrients in controlling feed intake in ruminants, in light of their particular anatomical, physiological, nutritional and behavioural characteristics. The ration is first digested in the rumen for several hours by microbial fermentation. Volatile fatty acids, which constitute 50–75 % of a ruminant’s energy supply, considerably depress feed intake when administered by short-term infusion into the rumen. However, this effect seems to be largely due to osmolarity problems. Only propionate seems to have a specific action, unrelated to osmolarity, in the mesenteric or portal veins. Nitrogenous nutrients have little short-term effect on feed intake, except when there is excess NH3 in the rumen. Metabolic cues from intestinal digestion, particularly of glucose and starch, have very little short-or long-term influence in controlling feed intake, in comparison with rumen digestion cues. However, the short-term responses in feeding behaviour do not always reflect longer-term effects on feed intake control. The effects of volatile fatty acid infusion on feed intake are much less significant over the long term, except in the case of propionate. The nutrients required for good microbial activity (proteins in the rumen) generally promote feed intake, whereas nutrients that disrupt rumen functioning (lipids) reduce feed intake. After a learning period, preferences are always governed by a tendency toward optimum rumen functioning, rather than by animal nutritional requirements, although the two factors are not independent. Ruminants, due to their particular anatomical and nutritional characteristics, have, in the course of their evolution, developed specific feed intake control mechanisms based on nutritional cues.Résumé L’objet de cette revue est d’étudier le rôle des nutriments dans les mécanismes de contrôle de la prise alimentaire chez les ruminants, en tenant compte de leurs particularités anatomiques, physiologiques, nutritionnelles et comportementales. La digestion de la ration se déroule d’abord pendant de nombreuses heures dans le rumen par fermentation des aliments par des microbes. Les acides gras volatils, qui constituent 50–75 % des nutriments énergétiques d’un ruminant, présentent des effets rassasiants marqués lorsqu’ils sont perfusés dans le rumen. Cependant, ces effets semblent liés dans une large mesure à des problèmes d’osmolarité. Seul le propionate semble agir avec une action spécifique autre que l’osmolarité au niveau des veines mésentériques ou porte. Les nutriments azotés ont peu d’effet à court terme sur la prise alimentaire, excepté en cas d’excès d’ammoniac du rumen. Les signaux métaboliques provenant de l’absorption intestinale, en particulier le glucose ou l’amidon, ont très peu d’effet, à court ou long terme, dans le contrôle de la prise d’aliment comparativement aux signaux provenant de la digestion ruminale. Mais les réponses observées à court terme dans le contrôle de la prise alimentaire ne présagent pas toujours des effets à plus long terme dans la régulation des quantités ingérées. Les effets des acides gras volatils sur les quantités ingérées sont beaucoup moins nets à long terme, sauf pour le propionate. Les nutriments indispensables au bon fonctionnement de l’activité microbienne (protéines dans le rumen) ont des effets favorables sur l’ingestion alors que les nutriments qui perturbent le fonctionnement du rumen (lipides) diminuent les quantités ingérées. Après apprentissage, les choix alimentaires s’orientent toujours vers une recherche d’un fonctionnement optimal du rumen plus que vers une bonne adéquation des apports aux besoins de l’animal, même si les deux ne sont pas indépendants. Les ruminants présentent donc, de par leurs spécificités anatomique et nutritionnelle, des adaptations originales dans les mécanismes de régulation des quantités ingérées à partir des signaux nutritionnels.
The effects of specific nutrients on the regulation of feeding behaviour in human subjects
- Stephen J. French
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- 28 February 2007, pp. 533-540
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Regulation of short-term energy intake involves the balance of positive drives to eat arising from the sight, smell and palatability of food with negative feedback signals from learned associations, gastrointestinal and metabolic signals. The stomach and small intestine are major sites in the feedback inhibition of food intake and subsequent period of appetite suppression. The present paper reviews the evidence that not only does the nature of the regulatory signal suppressing food intake depend on the type and energy content of nutrient consumed, but also the specific chemical composition of the nutrients and the site at which they are delivered. It is evident that feedback inhibition of feeding can be modulated by the particular chemical structure of nutrients (e.g. specific sugar or triacylglycerol structures). These differences in response are likely to be a consequence of differences in physical properties of particular nutrients depending on their chemical structure, and may also result from different receptor affinities for specific dietary structures. Moreover, the site of administration of nutrients can also profoundly affect the size and nature of the subsequent feeding response, suggesting that feed-forward interactions occur between the taste of foods and gastrointestinal stimulation.
Symposium on ‘Lipogenesis in farm animals’
Present and future studies on lipogenesis in animals and human subjects
- Richard G. Vernon, Michael C. Barber, Maureen T. Travers
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- 28 February 2007, pp. 541-549
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Lipogenesis occurs in all vertebrate species and has a critical role in energy balance, providing a means whereby excess energy can be stored as a fat. The metabolic pathways involved and their tissue distribution in different species, including man, are well known. The responses of lipogenesis to diet and to physiological and pathological states have been the subject of many studies. At a molecular level the major rate-controlling enzymes have been identified and their acute, and to a lesser extent chronic, control by hormones have been investigated extensively. However, there is no reason to suppose that all factors regarding lipogenesis have been identified (e.g. the recent discovery of acylation-stimulating protein). Little is known about the movement of newly-synthesized triacylglycerols in cells, either for secretion or storage. The production of leptin and tumour necrosis factor α by adipocytes provides a novel means of feedback control of triacylglycerol production, leptin by decreasing appetite and tumour necrosis factor α by inducing insulin resistance. The synthesis of these peptides appears to vary with the amount of triacylglycerol in adipocytes, but the molecular basis of this process is unknown. Elucidation of the signalling systems involved in the acute and chronic regulation of lipogenesis is also important, both with respect to some homeorhetic adaptations and also in some pathological conditions (e.g. non-insulin-dependent diabetes). Finally, molecular biology is revealing unexpected complexities, such as multiple promoters and different isoforms of enzymes (e.g. acetyl-CoA carboxylase; EC 6.4.1.2) exhibiting tissue specificity. Molecular biology, through transgenesis, also offers novel and powerful means of manipulating lipogenesis.
Symposium on ‘Functionality of nutrients and food safety’
Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects
- Baukje de Roos, Janet K. Sawyer, Martijn B. Katan, Lawrence L. Rudel
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- 28 February 2007, pp. 551-557
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Cafestol and kahweol, coffee lipids present in unfiltered coffee brews, potently increase LDL-cholesterol concentration in human subjects. We searched for an animal species in which cafestol similarly increases LDL-cholesterol. Such an animal model could be used subsequently as a model to study the mechanism of action of cafestol and kahweol. Cafestol and kahweol increased serum lipids in African green monkeys (Cercopithecus aethiops), cebus (Cebus apella) and rhesus (Macaca mulatta) monkeys, hamsters, rats and gerbils differently from the increase in human subjects. In African green monkeys, the rise in total cholesterol was less pronounced than that in human subjects. In addition, the increase in total cholesterol was predominantly due to a rise in HDL-cholesterol rather than LDL-cholesterol. Thus, the rise in plasma lipids might illustrate the mechanism in these monkeys rather than the mechanism in human subjects. In other animal species, cafestol and kahweol did not raise cholesterol consistently. The variability in effects on serum lipids could not be explained by the mode of administration or dose of diterpenes, nor by the amount of cholesterol in the diet. In conclusion, we did not find an animal model in which cafestol and kahweol elevate plasma lipoproteins to the same extent as in human subjects. For the time being, therefore, studies on the mechanism of action should be done preferably in human subjects.
Oxidant stress: the role of nutrients in cell-lipoprotein interactions
- Denis Blache, Laurence Gesquière, Nadine Loreau, Phillipe Durand
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- 28 February 2007, pp. 559-563
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Oxidant stress is increasingly becoming an important hypothesis to explain the genesis of several pathologies, including cancer, atherosclerosis and also ageing. Beside a few rare genetic defects, dietary factors are thought to play a key role in the regulation of the production of reactive oxygenated species. An imbalance between nutrients, and in particular those involved in antioxidant status, could explain the onset of an enhanced production of free radicals. We will briefly review information concerning oxidation of lipids and lipoproteins which lead to atherothrombosis. We also present new findings supporting a role for blood platelets in generating oxidant species. New data are also described concerning the role of oxygenated derivatives of cholesterol, oxysterols, in cellular cholesterol efflux and NO production. Also, new developments relating to the influence of direct effects of free radicals on cellular cholesterol homeostasis are presented. Finally, the in vitro effects of butyrate, a natural short-chain fatty acid produced by bacterial fermentation, in the protection against free radical-mediated cytotoxicity are discussed. These data provide information on the mechanisms of dietary antioxidants in preventing oxidant stress.Résumé Au côté des rares cas d’origine génétique, les facteurs nutritionnels (déséquilibres alimentaires, déficience en nutriments antioxydants) jouent des rôles cruciaux dans la modulation de la production d’espèces actives de l’oxygène, conduisant à l’établissement d’un stress oxydant, situation métabolique de plus en plus reconnue comme susceptible d’être à l’origine de nombreuses pathologies comme les cancers, l’athérosclérose et également le vieillissement. Après avoir brièvement rappelé les données concernant l’oxydation des lipides et des lipoprotéines susceptibles de conduire au développement de l’athéro-thrombogenèse, nous présentons des données récentes et originales indiquant que les plaquettes sont en fait capables à l’instar d’autres cellules, de produire des formes actives de l’oxygène susceptibles de modifier les LDL. Des résultats originaux sont également exposés concernant l’effets des oxystérols, produits d’oxydation du cholestérol générés au cours de l’oxydation des LDL ou présents dans l’alimentation, sur deux paramètres importants comme l’efflux du cholestérol cellulaire et la production de monoxyde d’azote. De plus, des données nouvelles relatives à l’effets du stress oxydant et son inhibition par des antioxydants d’origine nutritionnelle sont exposées sur l’homéostasie du cholestérol cellulaire. Enfin, dans ce contexte, les effets potentiellement antiathérogènes d’un acide gras à courte chaîne produit par la fermentation bactérienne, le butyrate, sont décrits sur la protection de cellules en culture vis-à-vis d’un stress oxydant in vitro. Ces éléments contribuent à apporter de nouvelles informations renforçant la notion de fonctionnalité des nutriments dans la protection du stress oxydant en relation avec la pathogenèse.
Metal ions as regulators of the conformation and function of the tumour suppressor protein p53: implications for carcinogenesis
- Catherine Méplan, Gerald Verhaegh, Marie-Jeanne Richard, Pierre Hainaut
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- 28 February 2007, pp. 565-571
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The p53 protein is a multi-function nuclear factor that is activated in response to multiple forms of stress and controls the proliferation, survival, DNA repair and differentiation of cells exposed to potentially genotoxic DNA damage. Loss of p53 function by mutation is a frequent event in human cancer, and is thought to result in the capacity of cells to acquire and accumulate oncogenic mutations during the progression of neoplasia. The p53 protein is a metal-binding transcription factor that is inactivated by metal chelation and by oxidation in vitro. In intact cells, p53 protein activity is crucially dependent on the availability of Zn ions and is impaired by exposure to Cd, a metal which readily substitutes for Zn in a number of transcription factors. Inactivation by Cd suppresses the p53-dependent responses to DNA damage. Overall, these findings indicate that regulation by metals plays an important role in the control of p53, and that perturbation of this control may explain the carcinogenic potential of several metal compounds. Résumé La protéine p53 est un facteur nucléaire multi-fonctionnel qui est activé en réponse à de multiples formes de stress et qui contrôle la prolifération, la survie, la réparation de l’ADN et la différenciation de cellules exposées à des agents génotoxiques. La perte de la fonction de p53 par mutation est un évènement fréquent dans les cancers chez l’homme, et l’on considère que cette inactivation a pour conséquence de rendre la cellule susceptible d’accumuler rapidement des mutations oncogéniques au cours de la progression du cancer. La protéine p53 est un facteur de transcription qui lie les métaux et qui peut être inactivée in vitro par chélation des métaux ainsi que par oxydation. Dans des cellules en culture, l’activité biologique de la p53 dépend de la bio-disponibilité en Zn, et est altérée par l’exposition des cellules au Cd, un métal qui se substitue facilement au Zn dans nombre de facteurs de transcription Zn-dépendants. L’inactivation de p53 par le Cd inhibe les réponses p53-dépendantes suite à la formation de lésions de l’ADN. Globalement, ces données suggèrent que la régulation par les métaux joue un rôle important dans le contrôle de la p53, et que des perturbations de ce contrôle pourraient contribuer à expliquer le potentiel carcinogénique de certains composés métalliques.
Micronutrients and ageing: intakes and requirements
- Marie-Jeanne Richard, Anne-Marie Roussel
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- 28 February 2007, pp. 573-578
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Ageing (and related diseases) may be described as a process which results from impaired immunological, genetic, neurological or endocrinological functions. Oxidative mechanisms may play an important role in the ageing process. It is important, therefore, to emphasize the relationship between health and nutrition in the elderly, particularly with regard to antioxidant micronutrient requirements. Indeed, accelerated ageing may be related to a deficit in the intakes of antioxidant vitamins (tocopherols, carotenoids and vitamin C) and trace elements (Zn and Se), as well as to an impaired adaptative mechanism against oxidative stress. Physiological modifications occurring during the lifetime and environmental influences are significant factors contributing to the impairment of micronutrient status, and these factors have to be considered when defining the specific requirements of the elderly. For Fe there is no evidence of benefit of supplementation in healthy subjects, but in the present state of knowledge combined supplementation, including Zn, Se, vitamins C and E and carotenoids, could be the best way to prevent accelerated ageing and reduce the risk of several common age-related diseases. Résumé De nombreuses théories (immunologique, génétique et neuroendocrinologique) ont été proposées pour expliquer les processus de vieillissement et les pathologies qui s’y rapportent. Les mécanismes oxydatifs pourraient contribuer à ces processus et plus particulièrement à leur accélération. La théorie radicalaire repose sur une modification avec l’âge du rapport prooxydants ou antioxydants dû à une majoration des processus oxydatifs accompagnés d’une diminution des systèmes de défense subséquentes à une carence en un ou plusieurs micronutriments antioxydants. Les modifications physiologiques qui accompagnent le vieillisement et une alimentation sélective contribuent aux modifications d’apport et d’absorption des micronutriments. Ces altérations sont accentuées lors de pathologies chroniques. Il n’existe pas de réel consensus sur les recommandations d’apports en oligoéléments adaptés au sujet âgé. Néanmoins les études récentes montrent qu’une association zinc, sélénium, vitamines antioxydantes (vitamines A et E et caroténodes) pourrait être le moyen le plus efficace de lutte contre les pathologies du grand âge et également de prévention du vieillissement accéléré.
Symposium on ‘Food technology: can it alter the functionality of nutrients’
Functionality of nutrients and thermal treatments of food
- Joël Hardy, Michel Parmentier, Jacques Fanni
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- 28 February 2007, pp. 579-585
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Since discovering fire man has used heat to modify the sensory properties and to preserve foodstuffs. Nutrients are involved in a number of reactions induced by this form of treatment. Some of these reactions are desirable, e.g. the improvement in the digestibility and the attractiveness of a food. Some reactions are undesirable because they lead to considerable nutritional loss or may result in the formation of mutagenic and carcinogenic molecules. The present paper reviews recent studies in which most of the modifications generated by thermal treatments at both the industrial and domestic level are demonstrated. We focus on the processes and the importance of thermal treatments used currently, as well as the necessity for optimization to minimize undesirable effects. Résumé L’homme a toujours recherché les moyens de développer ou modifier les propriétés sensorielles des aliments. Certaines sont souhaitées (amélioration de l’attractivité de l’aliment, meilleure digestibilité), d’autres sont proscrites en raison de la perte de qualité nutritionnelle ou de l’apparition de substances mutagènes et carcinogènes, par exemple. Cet article est une compilation des plus récents travaux sur les modifications générées par les traitements thermiques des aliments, tant au niveau industriel que domestique. Il insiste particulièrement sur les process. En conclusion, l’importance des traitements thermiques est aujourd’hui confirmée, mais il convient de poursuivre l’optimisation des procédés afin de réduire les effets indésirables.
Evaluation of the impact of food technology on the allergenicity of cow’s milk proteins
- M. Heyman
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- 28 February 2007, pp. 587-592
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The quantitative evaluation of the allergenicity of food proteins and the clinical tolerance towards antigens are problems the food industry and the clinicians have to face. The allergenicity of a protein depends on multiple factors, including the stability to digestion and the interaction with the intestinal environment. In addition to the possible reduction in allergenicity by technological treatments such as heat and enzymic hydrolysis, the complex interactions existing between the antigens, the intestinal epithelium and the underlying immune system, as well as the individual susceptibility to the sensitizing epitopes, have to be taken into account. Indeed, the intestinal cells are able to take up and process proteins, and possibly to present them directly to mucosal lymphocytes. On the other hand, pathophysiological conditions can modify the interactions between food antigens and the immune system. A large number of methods has been developed to assess the residual antigenicity of food proteins, based on the various immune responses leading to intestinal or extradigestive pathologies. Thus, the difficulty in measuring the residual allergenicity of hypoallergenic formulas is partly due to the physiology of the gastrointestinal tract, since an intricate network of interactions between enterocytes and immune cells governs the development of the immune response to food antigens. RésuméL’évaluation de l’allergénicité des aliments et leur bonne tolérance clinique est une question touchant à la fois les industriels de l’agro-alimentaire et les cliniciens. L’allergénicité d’une protéine dépend de multiples facteurs parmi lesquels la résistance à la digestion, les interactions avec le tractus digestif et les facteurs environnementaux. L’allergénicité d’un produit alimentaire peut être modifiée non seulement par les traitements technologiques industriels, mais aussi par le tractus gastrointestinal. La susceptibilité individuelle aux epitopes peptidiques formés est également un facteur primordial. En effet, les interactions complexes existant entre les antigènes, l’épithelium intestinal et le système immunitaire muqueux peuvent conduirent à des réponses immunitaires différentes selon les individus. De nombreuses méthodes existent pour mesurer l’antigénicité résiduelle des aliments, basées sur la nature des différentes réactions immunitaires anormales conduisant à une pathologie intestinale ou extradigestive. La difficulté de mesurer l’allergénicité résiduelle de formules hypoallergéniques repose donc sur les relations complexes entre les antigènes alimentaires, l’épithelium intestinal et le système immunitaire muqueux.
Targets and procedures for altering ruminant meat and milk lipids
- D. Demeyer, M. Doreau
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- 28 February 2007, pp. 593-607
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Beef and dairy products suffer from a negative health image, related to the nature of their lipid fraction. Rumen lipid metabolism involves the presence of saturated lipids in ruminant tissues. Lipolysis, fatty acid biohydrogenation and formation of microbial fatty acids in the rumen and their effects on rumen outflow of fatty acids are discussed. Special emphasis is given to the formation of trans-fatty acids and the possibilities of decreasing biohydrogenation. Small differences in intestinal digestibilities of fatty acids are mentioned, followed by a discussion on transfer of absorbed fatty acids into milk and adipose tissue lipids. The preferential retention of polyunsaturated fatty acids as well as the balance between synthesis and incorporation of fatty acids in tissues is described. Dietary means for the modification of milk fat are listed, with special emphasis on the possibilities for enrichment in polyunsaturated fatty acids and the presence of conjugated linoleic acids. A description of the nature and development of fat depots in beef cattle is followed by a discussion of breed, conformation and feed effects on adipose tissue distribution and fatty acid composition. Special emphasis is given to the very lean Belgian Blue double-muscled breed. The review ends with a consideration of the limits to the modification of ruminant fats, involving considerations of consumer acceptance as well as animal welfare and environmental effects.
Symposium on ‘Functionality of nutrients and gene expression’
A genetic dissection of the retinoid signalling pathway in the mouse
- Manuel Mark, Norbert B. Ghyselinck, Olivia Wendling, Valérie Dupé, Bénédicte Mascrez, Philippe Kastner, Pierre Chambon
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- 28 February 2007, pp. 609-613
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To determine the functions of retinoic acid receptors RAR and RXR, we have systematically knocked-out their genes by homologous recombination in the embryonic stem cells and generated null-mutant mice. This approach has allowed us to perform a genetic dissection of the retinoic acid signalling pathway.
The long-term consequences of intra-uterine protein malnutrition for glucose metabolism
- Susan E. Ozanne, C. Nicholas Hales
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- Published online by Cambridge University Press:
- 28 February 2007, pp. 615-619
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Our initial observations, in epidemiological studies, linking indices of poor early (fetal and infant) growth to the subsequent development of poor glucose tolerance and the insulin resistance syndrome in adult life, have been confirmed in studies in a wide variety of populations around the world. These findings led us 5 years ago to propose the ‘thrifty phenotype’ hypothesis. Tests of this hypothesis in an animal model in which the pregnant and/or lactating rat dams are fed on an isoenergetic diet containing just under half the normal protein content are consistent with the ideas put forward. They have also allowed us to refine the hypothesis in the light of the new data as follows: (1) the growth of the fetus (and possibly infant) is quantitatively and qualitatively altered by its nutritional environment (which may include maternal diet-dependent changes in maternal hormones); (2) these changes serve to select between the growth rates of different tissues according to priorities which differ between males and females (nutritional thrift) and to alter organ function to constitute a thrifty offspring adapted to survival in poor nutritional circumstances (thrifty phenotype); (3) an individual so constituted suffers adverse consequences in adult life if he/she experiences good or supranormal nutrition; (4) both poor insulin secretion and insulin resistance can result from these adaptive processes; (5) the adverse consequences include loss of glucose tolerance and hypertension. The precise outcome of growth retardation during early life may vary according to the type and timing of the factors responsible for the retardation. It remains to be determined to what extent these potentially adverse effects can be delayed or prevented by a suitable postnatal diet. Experiments in animal models are largely consistent with the concepts proposed from human epidemiological studies. They show that the metabolism of the liver, muscle and adipose tissue may be programmed by maternal nutrition during gestation and lactation. The combination of early growth restriction and subsequent adult obesity reproduced in the rat are the main features of the insulin resistance syndrome.
Regulation of gene expression by glucose
- P. Ferré
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- 28 February 2007, pp. 621-623
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Fatty acid synthase (EC 2.3.1.85) is an enzyme involved in the lipogenic pathway allowing fatty acid synthesis from glucose. Glucose up-regulates the transcription of the fatty acid synthase gene in both adipocytes and hepatocytes, with insulin having only an indirect role. The signal metabolite could be glucose-6-phosphate rather than glucose itself. The glucose response element of the fatty acid synthase gene has not yet been precisely identified, although a −2 kb region of the fatty acid synthase promoter is sufficient to confer nutritional responsiveness to a reporter gene. ADD1/SREBP1, a b-HLH-LZ transcription factor belonging to the sterol regulatory element-binding protein family might be involved in the transduction of the glucose effect. Finally, the stimulatory effect of glucose on the expression of the fatty acid synthase gene is inhibited by the activation of AMP-activated protein kinase. Interestingly enough, AMP-activated protein kinase is structurally and functionally related to the yeast SNF1 protein kinase complex which is essential for the transcriptional activation of glucose-repressed genes in Saccharomyces cerevisiae.
Amino acid limitation regulates gene expression
- Alain Bruhat, Céline Jousse, Pierre Fafournoux
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- 28 February 2007, pp. 625-632
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In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.
Selectivity of fatty acids on lipid metabolism and gene expression
- Thierry Raclot, Hugues Oudart
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- 28 February 2007, pp. 633-646
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Triacylglycerols represent the main form of storage for a wide spectrum of fatty acids. Their utilization first involves mobilization from adipose tissue through lipolysis. The release of individual fatty acids from adipose tissue is selective in vitro and in vivo in animal studies and also in human subjects. Generally, fatty acids are more readily mobilized from fat cells when they are short-chain and unsaturated. This selectivity could affect the storage of individual fatty acids in adipose tissue, and their subsequent supply to tissues. The nature of the dietary fats could affect lipid homeostasis and body fat deposition. Dietary fish oil influences adipose tissue development in a site-specific manner as a function of diet and feeding period. A diet high in n-3 polyunsaturated fatty acids (PUFA) results in a preferential partitioning of ingested energy towards oxidation at the expense of storage. Fatty acids are important mediators of gene expression in the liver. Indeed, genes encoding both glycolytic and lipogenic enzymes and key metabolic enzymes involved in fatty acid oxidation are regulated by dietary PUFA. White adipose tissue could also be a target for PUFA control of gene expression. The treatment of pre-adipose cells by fatty acids induces the expression of numerous genes that encode proteins involved in fatty acid metabolism. The mechanisms of PUFA-mediated repression of gene expression in adipocytes seem to be different, at least partly, from those described in liver. Tissue-specific and site-specific factors are possibly involved in the specific effect of PUFA on gene expression, although other mechanisms cannot be excluded.
Sir David Cuthbertson Medal Lecture
The impact of dietary protein restriction on insulin secretion and action
- Mark J. Holness
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- 28 February 2007, pp. 647-653
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The goal of this review is to develop the hypothesis, and review the evidence, that protein restriction, through synergistic effects on multiple organ systems predisposes to loss of normal regulation of fuel homeostasis that plays the central role in the development of type 2 (non-insulin-dependent) diabetes mellitus. The ability of insulin to regulate glucose production and disposal varies between individuals. These differences, together with the various compensatory mechanisms that are invoked to attempt to normalize fuel homeostasis, are of fundamental importance in the development and clinical course of type 2 diabetes mellitus. Protein deprivation impacts on both insulin secretion and insulin action. These effects may persist even when a diet containing adequate protein is presented subsequently. Data are presented that suggest that protein restriction results in an impaired ability of pancreatic β-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. This persistent impairment of insulin secretion resulting from protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of a diabetogenic challenge. This inability to maintain the degree of compensatory hyperinsulinaemia necessary to prevent loss of glucose tolerance may have relevance to the increased incidence of diabetes on changing from a nutritionally-poor diet to a Western diet, and to the hypothesis that some cases of type 2 diabetes in adulthood may be related to poor early nutrition.
BAPEN Symposium on ‘Artificial nutrition support: no longer an expensive luxury!!’
Outcomes of undernutrition in patients in the community with cancer or cardiovascular disease
- Jackie Edington, Paul D. Winter, Steve J. Coles, Catharine R. Gale, Christopher N. Martyn
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- Published online by Cambridge University Press:
- 28 February 2007, pp. 655-661
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Public health concern has tended to focus on the dangers of obesity, but there is evidence that undernutrition may also pose a risk to physical and mental well-being, particularly in those who are already ill. Using the General Practice Research Database (see office for Population Censuses and Surveys, 1995), we followed up 10 128 men and women aged 18 years and over who had been diagnosed with cancer or cardiovascular disease to examine whether nutritional status, as indicated by BMI, affected rates of use of health care resources and mortality. In both diagnostic groups, patients with a BMI below 20 kg/m 2 had higher rates of consultation with GP, higher rates of prescription and higher death rates during the follow-up period compared with those with a BMI of 20 – < 25 kg/m 2. In men and women with cardiovascular disease, poor nutritional status was associated with a sharply increased risk of hospital admission. Patients whose BMI was 30 – <40 kg/m 2 also tended to have increased rates of GP consultation and prescription, and if they were under the age of 65 years, they had an increased risk of death. The results of the present study suggest that in men and women with cancer or cardiovascular disease, even minor degrees of undernutrition are associated with a marked increase in morbidity and mortality.
Clinical Nutrition and Metabolism Group Symposium on ‘Nutrition and antioxidants’
Antioxidants and lipoprotein metabolism
- Mridula Chopra, David I. Thurnham
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- Published online by Cambridge University Press:
- 28 February 2007, pp. 663-671
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Lipoprotein metabolism plays a significant role in the pathogenesis of atherosclerosis and risk of vascular disease. Elevated levels of LDL and low levels of HDL are linked to the risk of cardiovascular disease. It is now widely accepted that oxidative modification of LDL affects the metabolism of lipoproteins, leading to their increased accumulation in arterial intima. The present paper will examine some of the accumulating evidence from studies showing relationships between dietary intake of antioxidant nutrients, i.e. vitamins E and C, the carotenoids and the flavonoids, and their influence on lipoprotein metabolism. In particular, the present paper will review the available literature on the affect of antioxidant supplementation on lipoprotein oxidation, and hence metabolism of LDL in human subjects.
Free radicals in skin and muscle: damaging agents or signals for adaptation?
- Malcom J. Jackson
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- Published online by Cambridge University Press:
- 28 February 2007, pp. 673-676
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Much of the current literature regarding the biological effects of antioxidant nutrients has concentrated on their potential role in inhibiting or preventing tissue damage induced by free radical species produced during metabolism. Recent findings indicate that antioxidants may also have more subtle roles, regulating changes in gene expression induced by oxidizing free radical species. There is increasing evidence that free radicals act as signals for cell adaptation in a variety of cell types and the nature of the mechanisms by which free radical species influence gene expression is the subject of much current research. Processes such as these may be particularly important in tissues regularly exposed to varying amounts of oxidative stress as part of their normal physiological functions. Examples of such tissues include skin exposed to u.v. light and skeletal muscle subjected to repeated bouts of exercise.