Phytoestrogens and bone

Symposia

S1-1 Nutrient Control of Food Intake

The protein leverage hypothesis in human

obesity

S.J. Simpson1_{; D. Raubenheimer} 2 1_{University of Sydney, Sydney, Australia;} 2_{University of Auckland, Auckland, New Zealand}

Background: The role of protein in the obesity crisis has, until recently, been largely ignored. This is for two reasons. First, protein provides the minor part of the human energy budget. Second, protein intake has remained far more constant over time and across populations than either fat or carbohydrate, both as a percentage of energy in the diet and in terms of absolute amounts eaten. Hence, while the obesity epidemic has spread, protein intake has remained relatively unchanged – giving the impression that protein cannot be responsible.

Method: We use state-space models (the Geometric Framework) developed from extensive animal studies to postulate a key role for protein appetite in the obesity epidemic, and provide supporting evi-dence from experimental, nutritional survey, and animal studies.

Results: Protein is the most satiating macronutrient group for humans and is the most tightly regulated post-absorptively. Results from comparative studies of other vertebrates, human experiments, and population-level data strongly suggest that the response of humans when faced with imbalanced diets is to prioritise protein intake. Hence, when the percent protein in the diet is low, non-protein energy is overeaten, whereas when dietary % protein is high, energy intake is limited: in both cases, absolute intake of protein is main-tained near constant.

Conclusion: We show how, paradoxically, it may be because pro-tein comprises a relatively small component of the human diet and is tightly regulated that it has sufficient leverage over human ingestive behavior to explain obesity. Focusing on this leverage over intake clarifies the role of dietary protein in the development of obesity, provides a possible means of ameliorating the problem, and explains the effectiveness of high-protein diets as weight loss regimes.

S1-2 Nutrient Control of Food Intake

Protein and weight regulation: theoretical

mechanisms and real observations

M.S. Westerterp-Plantenga

Maastricht University, Maastricht, The Netherlands; TIFN, Wageningen, The Netherlands

Recent findings suggest that an elevated protein intake seems to play a key role in body weight management, through increased sati-ety, wherein different proteins show different satiating efficiencies, and its effect on thermogenesis, body composition and decreased energy efficiency. The different satiating efficiences appear as

sig-nificant differences in subsequent energy intake during a testmeal, and even beyond. Relationships of satiety or subsequent energy intake with some ‘satiety’ hormones appear. Most of the factors mentioned are related to protein metabolism. Supported by these mechanisms, relatively larger weight loss and subsequent improved body weight maintenance have been observed following high protein diets. Increased insulin sensitivity may occur but it is unclear whether this is due to weight loss or type of diet. Under conditions of weight main-tenance, a high protein diet shows a reduced energy efficiency related to the composition of the body weight regained. A high protein diet during negative energy balance and during weight maintenance there-after preserves, or increases Fat Free Mass and reduces Fat Mass, thus improving the metabolic profile.

Since protein intake is studied at different energy intakes, absolute and relative protein intake needs to be discriminated. In absolute terms (grams per day), a normal protein diet becomes a relatively high protein diet if combined with negative energy balance and at weight maintenance. Therefore, ‘high protein negative energy balance diets’ aim to keep the grams of proteins ingested at the same level as con-sumed at energy balance, despite lower energy intakes.

S1-3 Nutrient Control of Food Intake

High protein diets: fact and fiction

Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen, UK

All weight loss strategies are based on some form of caloric defi-cit, whether by dietary control or increased physical activity or in combination [1]. Reducing body weight requires a reduction in energy intake relative to requirements. Although this is a simple mes-sage, in practice, maintaining caloric restriction is difficult. Altering the macronutrient content of the diet in order to achieve lower calorie intake is a popular means of attempting to achieve weight loss. High-protein diets appear to improve satiety relative to lower-High-protein diets, during dieting [2–3]. More recently, there has been renewed public interest in the use of high protein, low-carbohydrate diets (HPLC). There are a number of nutritional concerns, however, about the impact of such diets on longer-term health [4]. Although the diets do promote weight loss, at least in the short-term [2–3], it is still unclear what mechanisms underly these effects. There are possible physiological (e.g. protein induced satiety) and psychological (e.g. rapid weight loss) reasons why HPLC regimes are popular. Recent studies have indicated that obese subjects consume less (p  0.02) energy ad libi-tum on a HPLC diet in comparison to a high-protein moderate carbo-hydrate (HPMC) diet. However, motivation to eat or hunger were different on these regimes, with subjects more hungry on the higher-CHO intake (p  0.014). So how do such diets cause satiety at lower intake? Two obvious mechanisms might be considered. First, the direct effect of high protein intake. Second, the interaction of the HP intake with the ketogenic state induced by the low-carbohydrate intake. It is not clear whether the ketotic state enhances or detracts from motivation to eat (hunger and appetite), and therefore ad libitum intake, when subjects are consuming a high protein diet. Although a ketogenic state is not absolutely essential for increased satiety (less

hunger and reduced caloric intake) on high protein diets, voluntary intakes appear to be greater when they include moderate (35–45% of calories) [5] as opposed to low (10% calories) [6] carbohydrate content. This suggests an involvement of ketone body metabolism. In terms of possible mechanism, it is well known that during insulinope-nia (e.g. type 1 diabetes) or hyperketonaemia (e.g. acute or prolonged fasting) that the normal reliance of the brain on glucose as the major energy substrate (97%) is reduced and instead ketones bodies can provide as much as 30–50% of the metabolic fuel. In consequence, investigators examining fasting have suggested that appetite suppres-sion is due to ketosis because the effect of anorexia parallels the appearance of ketones in the blood and urine [7]. To date, however, no one appears to have conducted structured measurement of dietary induced ketosis, under conditions of a high-protein diet.

Weight loss should improve mortality or morbidity. Data suggest that HPLC diets can improve metabolic health parameters, at least in the short term [2–3]. For example insulin sensitivity, can be improved with HPLC diets with no detrimental effects noted on lipid profile. However, there is a paucity of data on how carbohydrate amount and type can impact on insulin sensitivity in subjects with obesity and metabolic syndrome. Other specific health parameters, such as the longer-term effect on gut health remain to be established. Certainly, short-term studies suggest that a low-carbohydrate diet can impact on bacterial populations resulting in a reduction in butyrate production (p  0.001), which has been implicated as being protective against colon cancer [8]. When considering this regime, the potential risks of a high-protein dietary weight loss strategy need to be weighed against the consequences of maintained excess adiposity or the ever-growing alternative of surgical intervention, as a longer-term solution to obe-sity.

Thus, control of intake by high protein diets and the involvement of ketogenic responses (through low carbohydrate provision) is a complex field, but one that is key to understanding how future diets might be constructed that help reduce caloric intake, yet still allow optimal nutrition in terms of longer-term health. From such knowl-edge, effective and healthy dietary strategies to tackle over-consump-tion of calories can be developed.

Acknowledgement

This work was supported by funding from the Scottish Executive Environment and Rural Affairs Department.

References

1 Garrow JS, Summerbell CD (1995). Eur J Clin Nutr. 49(1):1–10. 2 Samaha et al. (2003) N Engl J Med. 348(21):2074–81. 3 Foster et al. (2003) N Engl J Med. 348(21):2082–90. 4 Bravata et al. (2003) JAMA. 289 (14):1837–50. 5 Stadler et al. (2003) FASEB. J. 17, Abstract 3244.

6 Skov et al. (1999). Int J Obes Relat Metab Disord. 23:528–536. 7 Bloom WL (1959) Metab. 8:214–220.

8 Duncan et al. (2007) App Environ Microbiol. 73(4):1073–78.

S2-1 Gene Variants and Response to Diets

Dietary fat and lipid metabolism

Lipid and Atherosclerosis Unit, Department of Medicine, Hospital Universitario Reina Sofia, University of Cordoba, Spain

Much of our knowledge about the relationship between lipid, lipoprotein metabolism and the development of atherosclerosis and cardiovascular disease is based on measurements in the fasting state essentially reflecting endogenous metabolism. Although such mea-surements remain the foundation of clinical assessment and an impor-tant basis for decisions regarding hypolipidemic interventions, it should be acknowledged that we spend a considerable amount of time in a nonfasting, postprandial state. Based on typical Western eating patterns, most people consume three or more meals a day, with each containing 20 to 70 g of fat. Except at breakfast, each of these meals is most likely consumed before plasma triacylglycerols (TG) have returned to baseline levels from the lipemic conditions resulting from the previous intake. Thus, humans spend the majority of their day time in a postprandial (fed) state, with a continual fluctuation in the degree of lipemia throughout the day. The postprandial state is a dynamic, non steady-state condition, with rapid remodeling of lipo-proteins compared with the relatively stable fasting condition. Determination of the postprandial response is complex, and it is, therefore, more challenging to assess the cardiovascular risk associ-ated with postprandial lipemia than during fasting conditions. In spite of this, it is becoming increasingly evident that future efforts to study and treat lipids related to atherogenesis should include postprandial parameters. Several clinical studies have shown that delayed elimina-tion of postprandial TRL is associated with atherosclerosis. There are also reports of an association between postprandial lipemic response and subsequent progression of atherosclerosis in patients with pre-existing CHD. The pathogenesis of the relationship between postpran-dial TRL and CHD remains unclear, but experimental evidence has provided several plausible mechanisms. Atherogenic effects may be mediated directly by TRL particles or components of the particles. A variety of in vitro and clinical studies suggest that postprandial chylo-microns and VLDL are associated with adverse effects on arterial endothelium. The aim of this presentation is to consider the regula-tory pathways of postprandial lipoproteins and the major factors including nutrition, life style, physiopathology and genetics which may contribute to inter-individual variability in postprandial lipaemia, and thereby, susceptibility to atherosclerosis.

Most of diurnal time is spent in a postprandial state due to succes-sive meal intakes along the day. As long as meals contain enough fat, transient increase in triglyceridemia and change in lipoprotein pattern occurs. Postprandial lipoprotein metabolism is modulated by back-ground dietary pattern as well as meal composition (fat amount and type, carbohydrate, protein, fiber, alcohol) and also several lifestyle conditions (physical activity, tobacco use), physiological factors (age, gender, menopausal status) and pathological conditions (obesity, insulin resistance, diabetes mellitus). Overall studies that have evalu-ated impact of habitual fat type on postprandial response to acute fat ingestion have shown that in terms of postprandial TG response effects are in the order SFA  MUFA  n-6 PUFA  n-3 PUFA.

The roles of many genes have been explored in order to establish the possible implications of their variability in lipid metabolism and

CHD risk. The postprandial lipid response has been shown to be modified by polymorphisms within the genes for apo AI, apo AIV, apo AV, apo E, apo B, apo CI, apoCIII, lipoprotein lipase, hepatic lipase, fatty acid binding and transport proteins, microsomal triglyc-eride transfer protein and scavenger receptor class B type I. Overall, the variability in postprandial response is important and complex, and the interactions between nutrients or diet or meal compositions and gene variants need further investigations. Extent of present knowl-edge and needs for future studies are discussed in light of on-going developments in nutrigenetics.

S2-2 Gene Variants and Response to Diets

Fat oxidative capacity in obese subjects

Department of Human Biology, Nutrition and Toxicology Research Institute, Maastricht, The Netherlands

Accumulation of lipids in skeletal muscle plays a critical role in the etiology of the obese insulin resistant state and type 2 diabetes mellitus by interference of lipid metabolites with insulin signalling. Muscle lipid accumulation, often under conditions of a high fat intake and/or a reduced physical activity, arises in the setting of high circu-lating free fatty acids and triacylglycerols. Adipose tissue is a major player in this systemic lipid overload, sequestering fatty acids in the postprandial phase and releasing them later on. In insulin resistance, the flexibility of adipose tissue to regulate dietary fatty acid trapping and endogenous lipolysis may be impaired, resulting in exposure of muscle to excessive fluxes of lipids. Furthermore, an impaired capac-ity to regulate muscle lipid turnover including an impaired switch between carbohydrate and fat oxidation may contribute to the accu-mulation of lipids within muscle. Interestingly, a recent study showed that the switching between substrates in vivo was preserved in human myotubes, seperated from their neuroendocrine environment, sug-gesting that this phenomenon is partly intrinsically determined. Also, we showed this impaired metabolic flexibility in prediabetic subjects, suggesting that this impairment may be an early factor towards the development of type 2 diabetes mellitus

In this presentation, the physiologic mechanisms responsible for channeling a ‘lipid overload’ to muscle as well the molecular mecha-nisms for directing the excess fatty acids to particular fates will be discussed. Also, attention will be paid to whether the disturbed mus-cle fat metabolism may be a primary genetically determined event and whether and disturbances can be reversed by means of nutritional intervention in parallel to improvements in insulin sensitivity.

S2-3 Gene Variants and Response to Diets

Genetic make-up and dietary-induced

weight loss

J.A. Martínez

Institute of Food Sciences and Nutrition, University of Navarra, Pamplona, Spain

Obesity is a complex disease, which in many cases appears as a polygenic condition affected by environmental factors (mainly unbal-anced dietary patterns and physical inactivity). In this context, the weight loss response to dietary interventions varies widely and pre-dictive factors of successful slimming are poorly understood includ-ing those concerninclud-ing the genetic make-up.

Indeed, a number of genes involved in the regulation of energy expenditure, appetite, lipid metabolism and adipogenesis have been reported to affect the risk of treatment failure in some obese subjects. Therefore, this review shows evidences from human studies that sup-port the existence of a genetic component in the fat reduction associ-ated to a negative energy balance.

Some candidate genes for the prognosis of weight loss response related to energy expenditure are those codifying for the adrenergic receptors and uncoupling proteins, while genes related to appetite potentially affected by energy restriction are leptin, leptin receptor, POMC and the serotonin receptor. Furthermore, adipogenic genes such as PPAR2 and genes related to lipid metabolism including hepatic lipase and lipoprotein lipase have been also related to the weight lowering outcome induced by hypocaloric diets. As a matter of fact, the following examples can be mentioned:

At position C-2549 A of the leptin gene, it was found a weaker •

body mass index reduction for 2549 A allele carriers than the observed for homozygotes for the 2549 C allele.

Resistance to lose weight in homozygous for the Arg64 allele of •

the 3 adrenergic receptor gene compared with higher reductions either in heterozygotes or Trp64 homozygotes.

The impact of energy-restriction may differently affect the ana-•

tomical area of the fat loss (Subcutaneous vs. visceral) as demon-strated in the Gln27Glu polymorphism of the 2-adrenergic receptor gene.

A relevant role for the A-3826G polymorphism of the UCP1 gene •

in the magnitude of weight loss has been suggested.

Some UCP3 polymorphisms were associated with the changes in •

mRNA levels and body weight loss.

A 3-year study showed that subjects with the Ala12Ala allele of •

the PPAR gene lost more weight than subjects with the other genotypes.

A IL-6 polymorphism (

• 174 G  C) may influence weight regain

after a weight-lowering program based on a energy-restricted diet, which may interact the Pro12Ala polymorphism of the PPAR- gene.

In the Finnish DPS, it was found that subjects with the G-250G •

promoter polymorphism of the hepatic lipase gene (LIPC) tended to loss less weight than subjects with the 250 A allele both in the control and in the intervention group

Additionally, a large scale European intervention trial (NUGENOB) •

concerning the comparison of the impact of more than 40 genetic polymorphisms on weight loss revealed that much work is required to be performed in this area, suggesting that the possibil-ity are enormous in this field.

Identification of additional candidate genes may allow providing ‘personalized’ specific recommendations (dietary advice, physical activity and/or drug therapy) to achieve effective weight loss and suc-cessful long-term maintenance of the slimming on the basis of an identified genetic susceptibility. Given the complexity of weight loss responses, supplementary efforts are needed to identify the interac-tions between the most relevant gene polymorphisms affecting both the amount and composition of the weight loss as well as the changes in obesity-associated risk factors depending of the characteristics of the nutritional strategy (energy deficit and dietary macronutrient dis-tribution). In the future, the advances in molecular genetic biotechnol-ogy will ease the way to combine the search for new candidate genes, novel polymorphisms, and gene expression patterns putatively involved in gene-nutrient interaction concerning weight homeostasis.

References

Goyenechea, et al: Weight regain after slimming induced by an energy-re-stricted diet depends on IL-6 and PPAR2 gene polymorphisms. Br J Nutr 2006;96:1–9.

Marti A, et al: Genes, lifestyles and obesity. Int J Obes 2004;28:29–36. Marti A, et al: Advances in molecular nutrition: nutrigenomics and/or

nutrige-netics. Nutr Hosp 2005;20:157–164.

Martínez JA, et al: Obesity risk is associated with carbohydrate intake in women carrying the Gln27Glu beta2-adrenoceptor polymorphism. J Nutr 2003;133:2549–2554.

Martinez JA, Body-weight regulation: causes of obesity. Proc Nutr Soc 2000;59:337–445.

Moreno-Aliaga MJ, et al: Does weight loss prognosis depend on genetic make-up? Obesity Reviews 2005;6:155–168.

Nieters A, et al: Polymorphisms in candidate obesity genes and their interac-tion with dietary intake of n-6 polyunsaturated fatty acids affect obesity risk in a sub-sample of the EPIC-Heidelberg cohort. Eur J Nutr 2002;41:210–221.

Rankinen T, et al: The human obesity gene map: The 2005 update. Obesity Res 2006;14:529–644.

Santos JL, et al: Genotype-by-nutrient interactions assessed in European obese women: A case-only study The NUGENOB consortium. Eur J Nutr 2006;45:454–62.

Sorensen TIA, et al: Genetic polymorphisms and weight loss in obesity: A randomised trial of hypo-energetic high- versus low-fat diets. The NUGENOB consortium. PLOS Clinical Trials 2006;1:e12.

Todorova B, et al: The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to type 2 diabetes mellitus: the FDP study. J Clin Endocrinol Metab 2002;89:2019– 2023.

Viguerie N, et al: Adipose tissue gene expression in obese subjects during low-fat and high-low-fat hypocaloric diets. Diabetologia 2005;48:123–31.

S3-1 Food Structure and Metabolic Consequences

Enzymatic food structure engineering

VTT Biotechnology, P.O. Box 1500, FIN-02044 VTT, Finland Food structure is a very important quality attribute in food choice, since it affects not only the sensory perception of texture, but also release of flavour. Food structure can also have impact on nutritional quality. Enzymes offer specific means to engineer food structure by creating cross-links to food biopolymers, i.e. to proteins and/or carbo-hydrates. The type of enzyme used affects the chemistry of the cross-link formed and subsequently the structure of biopolymer networks of

the food product. Enzymatic cross-linking of food biopolymers can be exploited to create novel types of structures to foods without any need of added food ingredients.

Different types of oxidative or non-oxidative enzymes can be exploited for cross-linking reactions. Among potential enzymes for protein crosslinking are transglutaminase and various oxidative enzymes, such as laccase, tyrosinase or peroxidase. These enzymes have different mode of action and thus the chemistry of crosslinking varies. Laccases and peroxidases can be used to crosslink ferulic acid containing carbohydrates, such as sugar beet pectin or arabinoxylan. Proteins can be crosslinked by different oxidative or transferase type of enzymes. Transglutaminases can crosslink proteins via formation of isopeptide linkage. Laccase and peroxidase can oxidize tyrosine residues to corresponding radicals, which in turn can further react with different groups in proteins. Tyrosinases, on the other hand, oxi-dize tyrosine to a quinone, which can further react with aromatic ring, amine and thiol groups present in proteins. The biopolymer networks formed can be further engineered by combining adequate processing to the enzyme treatment. In this work the potential of enzymatic food structure engineering is reviewed with special emphasis on dairy, bak-ing and meat applications.

S3-2 Food Structure and Metabolic Consequences

Role of food structure in starch digestibility

and glycemic response

F. Brighenti

Department of Public Health and Department of Internal Medicine and Biomedical Science, University of Parma, Parma, Italy

Abstract not received.

S3-3 Food Structure and Metabolic Consequences

Molecular approaches to understanding

gastrointestinal digestion of proteins

Little is known regarding the breakdown of proteins in the gastro-intestinal tract at a molecular level, or the effects food structures, such as colloids, have on this. However, such an understanding is essential to understanding what makes a protein become an allergen, and the oral delivery of bioactive proteins and peptides in foods.

It has been proposed by that protein digestibility (measured as resistance to pepsin) is one of the relevant parameters used for the assessment of the allergenic potential of novel proteins. However, these systems do not mimic those found in vivo in the gastrointestinal tract and frequently neglect the role of the food matrix and structure on digestion. It is also becoming evident that the majority of food allergies are caused by a relatively small number of structural types of

allergens. One explanation maybe that the structural features and biological properties shared by food allergens can affect their behav-iour in the gastrointestinal tract, potentiating their allergenicity com-pared with non-allergens. We have been systematically studying members of two important plant food allergen families, the prolamin superfamily (the non-specific lipid-transfer proteins from grape and 2S albumin allergen form Brazil nut) and the cupin superfamily (the 7S storage protein allergen from peanut, Ara h 1). We have shown that the prolamin superfamily scaffold, comprising a disulphide-linked scaffold with intertwining -helices, is highly stable to digestion and retains its IgE-binding epitopes even after simulated gastro-duodenal digestion. However, the hypothesis that resistance to digestion is important fro allergenicity does not appear to hold true for cupin superfamily allergens, which have been shown by proteomic methods, to be extensively degraded to low molecular weight peptides of less than 3,000 Da. However, these peptide aggregates retain their aller-genic potential. Other factors, such as peptide aggregation and adju-vant effects of other food components, may play a role in stimulating IgE responses to these allergens.

S4-1 Pollutants in the Food Chain

Endocrine disruptors: large effects from

small exposure

Jean-Pierre Cravedi

INRA, UMR 1089, Xénobiotiques, BP 3, 31931 Toulouse Cedex 9, France

Endocrine disruptors are generally described as substances with anti-oestrogenic, oestrogenic, anti-androgenic or androgenic effects. More recently, other targets have been evidenced such as the thyroid and immune system. Many different endocrine disruptors are present in the various compartments of the environment (air, water and land) and in foods (of plant and animal origin). They may originate from food packaging, combustion products, plant health treatments, deter-gents and the chemical industry in general. In addition to the potential effects of these compounds on adults, the sensitivity of embryos and foetuses to many of the xenobiotics likely to cross the placenta has raised considerable concern and led to major research efforts. With the exception of the clearly established links between diethylstilbe-strol, reproductive health abnormalities and cancers, very little is known for certain about the effects of endocrine disruptors on human health. Given the lack of available data, current concerns about the possible involvement of endocrine disruptors in the increase in the incidence of breast cancer, and possibly of endometriosis and early puberty in girls, remain hypothetical. Conversely, the deterioration in male reproductive health is at the heart of preoccupations and prog-ress in analyses of the relationship between endocrine disruptors and human health. This presentation aims to describe the current state of knowledge about endocrine disruption, focusing in particular on the problem of contaminants present at low levels in food commodities.

Acknowledgment

Part of this work was funded by EU Cascade network (Food-CT-2003-506319).

S4-2 Pollutants in the Food Chain

Residues of pesticides in food: Cause of

concern?

Nicolas Olea; Mariana F. Fernández

Hospital Clinico-Univ of Granada, Granada, Spain

Organochlorine pesticides (OCs) are highly toxic man-made chemicals that persist in most environmental compartments, e.g., atmosphere, soil, water, sediments and biota. Industrialized nations have restricted or banned many OCs, but they continue to be manu-factured for export. Many OCs are persistent and lipophilic, favouring their accumulation in fat tissues. OC exposure is mainly via food, especially fruit, vegetables, meat and dairy products, and can be related to regional activities, e.g., the extensive greenhouse agricul-ture in Southern Spain. Children can be exposed to OC pesticides in utero via the placenta and post-delivery via contaminated breast milk or infant formula. Children usually eat more fruit and vegetables versus adults, increasing the risk of exposure via contaminated food. Exposure risk of children may also be increased by their tendency to explore the environment with their mouths, their closeness to the ground and their increased time playing outdoors, and by their con-sumption of a larger amount of food and water relative to body weight versus adults. The presence of OC pesticide residues in adult and children in areas with greenhouse agriculture was recently reported by our group. There is limited evidence on the long-term human health effects of chronic OC exposure. OCs have been linked to some human endocrine disorders, e.g., cryptorchidism and sexual precocity, and are highly toxic to the nervous system, especially during early development stages. Parental occupational and childhood exposure to pesticides has also been associated with some forms of cancer.

S4-3 Pollutants in the Food Chain

Developmental neurotoxicity from food

contaminants

P. Grandjean

Institute of Public Health, University of Southern Denmark, Odense. Denmark

Abstract not received.

S5-1 Double Burden of Malnutrition

IUNS malnutrition task force

Department of Nutrition, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7590, USA

S5-2 Double Burden of Malnutrition

Transition from undernutrition to obesity

Training and Research Unit on Food Sciences, Laboratory of Physiology Applied to Nutrition and Feeding, Chouaib Doukkali University,

School of Sciences, El Jadida, Morocco

Although the African Region has not yet overcome the problems of undernutrition, it is increasingly facing additional challenges related to industrialization and urbanization leading to disabilities and death globally and in developping countries, what is called Nutrition Transition. Indeed nutrition-related chronic diseases combined with certain changes in lifestyles can lead to the onset of cardiovascular (CHD) disease. These factors generically called risk factors, are smoking, lack of physical activity, diet, hypertension, hypercholester-olemia, glucose intolerance and obesity.

Prevalence of undernutrition

In Morocco an African country, data on anthropometric satatus in children under five years, show that both under-nourishment and overweight are prevalent. In fact 24% of children were stunted and 9% underweight while 9.2% were overweight (9.5% boys and 8.8% girls). In Adults anthropometric status data show a prevalences of 9.8% for undreweight and 21.4% for overweight (16.9% men and 25.5% women) and 4.1% for obesity (1.6% men and 6.4% women) were registered in 1984. These prevalences decreased for underweight and increased for overweight and obesity in the year 1998. Indeed 4.7% were underweight; 27.1% overweight (21.1% men and 29% women) and 11.7% were obese (4.3% men and 16% women). The prevalence of cardiovascular diseases risk factors are also increased comcomitently to micronutrients deficiency. The last national survey results show a high prevalence of anaemia and iron deficiency in women and children with either depleted or low iron stores. Iodine deficiency was also reported in schoolchildren and women.

Prevalence and trend of obesity in adults

Data on prevalence of adult obesity have not been well docu-mented at a national level in all African countries. The most compre-hensive data of national trends in the prevalence of obesity in Northafrica for example come from Morocco, Egypt and Tunisia where obesity show alarming trends.

In these countries, an evident sex and geographical variation in the prevalence of adult obesity was reported between 1984 and 2000. The highest rates of obesity are observed in Egypt where average BMI in urban women rose from 27.7 to 30 kg/m² in national surveys con-ducted between 1994 and 1998/99. The prevalence of obesity was 45% in urban Egyptian women in 1998 and more than 20% among rural women and men. In Morocco obesity rose from 6.4% to 22% in women against 1.6% to 8% in men. In Tunisia, the prevalence of overweight and obesity increased from 28.3% in 1980 to 51% in 1997. In 1996–1997, the prevalence of obesity was 22.7% in women and 6.7% in men and the prevalence of abdominal obesity was 9% in men and 33% in women. In Libya the overall prevalence of over-weight was 59.4% between 1981 and 1990 while a large-scale study carried out in six provinces in 1999 revealed that more than one out

of five women were overweight and 7% were obese. In Mauritania, data from national survey conducted in 1989/90 reported prevalence of overweight in 36% and obesity in14% of women of more than 18 years old. In Algeria, overweight prevalence of 46% was reported by the only one rural Regional survey realized in 1993 on adults women aged 15 years and older.

According to WHO Global InfoBase, north Africa now has one of the highest average BMI of all WHO Regions and the prevalence of obesity among women is higher than reported for women in most industrialized countries. In 2002, the levels of obesity ranges from 11.9% in Algeria to 39% in Egypt among women and range from 2.9% in Mauritania to 22% in Egypt among men. After only three years, in 2005, a progressive increase of obesity prevalence in the Region is clearly observed; the levels of obesity ranges from 13.4% in Algeria to 45.5% in Egypt among women and range from 3.7% in Morocco and in Mauritania to 22% in Egypt among men.

It is expected that in 2010, obesity rise among men in Algeria, Mauritania and Libya, and among women in all six north African countries. In all north African countries, obesity was more prevalent in urban than in rural areas, varies by geographical residence, posi-tively associated with age and negaposi-tively with education level.

Prevalence and trend of childhood obesity

Overweight and obesity prevalence among children is increasing worldwide and may be associated with increased risk for the develop-ment of obesity and chronic diseases in adulthood. The few available data of national representative surveys show also that childhood obe-sity is a matter of growing concern in north Africa. De-Onis and Blössner reviewed the prevalence of overweight among preschool children (0–5 years) in 94 countries (1) and revealed that within the UN subregions, the highest rate of overweight preschool children was in North Africa (8.1%), driven mainly by Algeria (9.2%), Egypt (8.6%) and Morocco (6.8%).

The prevalence of overweight continues to increase in the Region during the school age and adolescent stages. According to the various studies, prevalence of body fat excess in school children and adoles-cents (6–18 years) is estimated to 9–18% and more common in girls than boys.

Health consequence of obesity in north Africa Obesity, caused by the ‘nutrition transition,’ has been identified as one of the leading risk factors for non-communicable mortality worldwide. In 2002 cardiovascular diseases (CVD) caused from about 34.3 to 52% of all deaths in north Africa, making it the major killer among non-communicable diseases. Indeed, research from north African countries shows that overweight and obesity impaired biliary lipid composition and increased the number of patients with cholesterol gallstones in Algerian women. Also, obesity increases the risk of hypertension and dislipidemia in Tunisian children and in Egyptian and Moroccan women. It is considered as principal causes of increased prevalence of diabetes and metabolic syndrome in Morocco, Tunisia and Libya.

Generally, in almost all of these African countries, CVD risk fac-tors increased with age, affected more women and urban area and were significantly associated with obesity (2).

Possible causes of obesity in Morocco

Many hypotheses have been proposed to explain the increase of the prevalence of obesity, ranging from the effects of excess of dietary intakes and low physical activity level. However, in women the com-bination of urban living and an abundant food supply does not provide the entire explanation of obesity. It is very likely that the cultural preference for female plumpness coupled with physical and cultural barriers to physical activity makes the difference.

Dietary habit in northern African countries

It is was reported that the high consumption of foods rich in fats and calories played an important role in the rise of obesity. This could be the case in northern African countries. Analysis of FAOSTAT data (3) shows that food consumption patterns and dietary habits in north-ern African Region have changed markedly during the past 3 decades. During 1964–2000, there has been a significant progress in raising food consumption accompanied by some structural changes and a great shift from traditional foods to more westernized foods, which are characterized by high fat, high cholesterol, high sodium and low fibre.

Sedentary lifestyle

Data on the northern African population demonstrated high level of sedentarity. Indeed a high percentage of the population have decreased physical activity at work and leisure by spending more hours per week watching TV and the utilisation of more vehicles and activity saving appliances. According to WHO Global InfoBase, about 32% of the population of 40–69 years old in Tunisia, about 26% of the population of 25–64 years old in Algeria and about 52% of the population aged 20 years and older in Egypt are inactive. Also, a survey conducted in 2002 among Moroccan women aged over 15 years, on the association between physical inactivity and cardiovascu-lar risk factors, indicated that physical inactivity appears to play a critical role in the development of body fat and may be a risk indica-tor for features of metabolic syndrome. Most of those women were involved in a traditional sedentary occupation and the time spent in the tradition of tea consumption and afternoon sleeping habits increased with the number of metabolic syndrome components. In the opposite, women without metabolic syndrome components tended to expend more energy (walking activity) than those with metabolic syndrome.

Furthermore, it is essential to signal that the marked physical inactivity observed among women could be explained by cultural and physical barriers.

Culture

Obesity management is a complex issue that includes not only dietary habits and physical activity, but also a wide range of cultural and psychosocial issues. Indeed, attitudes toward body weight and preferences for a particular level of fatness are mediated by local sociocultural factors, which could explain the difference in the per-ception of body weight between population subgroups. In some African societies where thinness is considered as a sign of starvation, fatness may be culturally valued as a welcomed sign of health, beauty, prestige, and prosperity. Several studies conducted in northern African countries have shown a traditional strong positive cultural views of large bodies.

Conclusion

Although obesity has become one of the major health problems in the Region, and it is associated with several chronic diseases, it is not recognized as a high public health priority in African countries, as they are still confronted with the heavy burden of infectious diseases and poor maternal and child health. Additionally, there is a great lack of quantitative and qualitative research and studies on obesity. There are a lack of knowledge about factors contributing to the occurrence of obesity and particularly about all economic, mental and physical costs associated with obesity in the Region. Such information are primordial for efforts to convince governments and health profession-als about the importance of the problem of obesity in social and economic terms, and may help to improve strategies for the manage-ment and prevention of obesity.

In order to achieve this, several objectives are essential for com-bating the epidemic. Policy-makers should first of all be aware of the cost of obesity that is a major contributor to total healthcare costs in affluent societies. Also, there is a need for a national programme in each country to increase obesity awareness, to prevent and control obesity. On the otherhand it is necessary to take in account the pres-ence of traditional norms of beauty in Africa that could limit the suc-cess of interventions aiming to reduce unhealthy body weight in women. Therefore, it is primordial to educate people in terms of weight complications management to develop behaviors that may promote healthier lifestyle and decrease probable risk factors associ-ated with overweight and obesity.

In brief, populations in Africa are suffering of both nutritional problems, deficiencies and chronic diseases indicating that these countries are undergoing rapid nutrition transition. Also, overweight and obesity, in African countries, are a cause of concern not only among adults, but also among children and adolescents and the rate of increase shows no sign of slowing. The need for a broad-based public education is obvious in the Region, and should be an urgent priority for the public health system.

References

1 de Onis M, Blössner M: Prevalence and trends of overweight among pre-school children in developing countries. Am J Clin Nut. 2000;72:1032– 1039.

2 Belahsen R, Rguibi M: Population health and Mediterranean diet in south-ern Mediterranean countries. Public Health Nutrition 2006:9:1130–1135. 3 FAO, 2005. Nutrition Country Profiles. http://www.fao.org/ag/AGN/

nutrition/profiles_by_country_fr.

S5-3 Double Burden of Malnutrition

Causes of worldwide obesity

Institute of Nutritional Sciences, University of Vienna, Austria

During the last decades, obesity has become an ever increasing health issue considering its weighty contribution to morbidity and mortality. Indeed, according to the World Health Organisation, nearly one third of the global population over 15 years were overweight in 2005 and 400 million obese. The prevalence of obesity is also rising

in children, especially in industrialised countries, ranging from 3.6 to 22 and 2.7 to 12.3 percent among European boys and girls under 16 years, respectively. The problem is, however, no longer confined to wealthy nations but is reaching developing countries as well.

Conceiving efficient measures to fight this epidemic requires the knowledge of the underlying determinants. Doubtless, modern seden-tary lifestyle and the wide availability of energy-dense, but micronu-trient-poor food are the leading causes of overweight. Traditional food is displaced by highly processed, refined products containing high amounts of added lipids and sugar. Increasing automation and motori-sation as well as passive leisure pastimes entail a decline in physical activity. Socio-economic factors also have an influence: While in former times, overweight was rather seen in wealthy people as it is still in many developing countries, it has become more frequent in lower social classes of modern industrialised societies. As the adipo-genic environment impacts differently on individuals, genetic differ-ences are also likely to play a role. Therefore, the general focus of intervention has to be on healthy diets and regular physical activity with individualised approaches taking into account the social environ-ment and possibly the genetic background.

S6-1 Gut Microbiomics and Nutrition

Intestinal metagenomics and nutrition

UEPSD – INRA, Jouy-en-Josas; Hôpital La Riboisière, Paris; Libragen S.A., Toulouse, France

Over the past century, the recognition of the diversity of the human intestinal microbiota had been based on anaerobic culture techniques. The past decade has allowed to draw a more complete phylogenetic picture based on molecular tools. Different approaches showed that over 80% of dominant phylotypes of the human adult faecal microbiota belong to only 3 phyla, the Bacteroidetes, Firmicutes or Actinobacteria. In addition, the vast majority is not represented in culture collections, the uncultured fraction rising from birth to the old age. Comparative studies indicated that the intestinal microbiota is stable over time and resilient upon antibiotic treatment. Two third of dominant species appears totally subject specific and a limited frac-tion appears all together more numerous and more prevalent, consti-tuting a phylogenetic core of the human intestinal ecosystem.

We are thus at present faced with two paradox: first, at the level of dominant species, the human intestinal microbiota is essentially subject-specific while it is expected to have a marked metabolic homogeneity between individuals; and second, it appears resistant to modifications while we have evidence of its modulability by func-tional foods. It is likely that the explanation lies at the level of the genome, proteome or metabolites of the microbiota. We have hence initiated global approaches to explore the functionalities of the intes-tinal microbiota at the level of its metagenome (gene repertoire) and metaproteome (protein repertoire).

The representativity of our first metagenomic libraries, generated from the bacterial fraction of the faecal microbiota, was assessed on a phylogenetic basis. Dominant phyla are recovered among the large genome fragments cloned. Sequence information indicates the

exis-tence of functionalities reminiscent of anaerobic adaptation, mucins and fibre degradation abilities, vitamin production, etc. Total cyto-plasmic proteins from the same bacterial fractions indicated the exis-tence of a large pool of common proteins, indicative of the exisexis-tence of a functional core of the human intestinal microbiota.

A series of functional screens was finally applied to metagenom-ics libraries, permitting the exploration of genetic resources that had remained essentially inaccessible until today. Our phenotyping results demonstrate the existence of a large variety of biopolymer converting enzymatic activities but also they allow the exploration of signal mol-ecules of the cross-talk between bacteria and human cells.

In a context where the contribution of the human intestinal micro-biota to nutrition and health is more and more recognized, metage-nomic and metaproteomic approaches appear highly promising to identify conserved genetic and proteic traits within the human intes-tinal microbiota and qualify its functional balance. They furthermore give access to functionalities and bioactive molecules with immense innovation potentials.

S6-2 Gut Microbiomics and Nutrition

Microbiomics of probiotic and other

intestinal bacteria

Willem M. de Vos

Wageningen and Helsinki University, The Netherlands and Finland

The microbial world within us includes an astonishing array of intestinal microbial communities, consisting of more than 1,000 spe-cies and dominated by gram-positive bacteria [1–3]. The dynamics of this microbial diversity in time and space has attracted considerable attention and we have contributed to this by developing and applying a phylogenetic microarray, termed the Human Intestinal Tract (HIT) Chip, to analyze colonization succession, community stability and diet-related community changes [4]. To link diversity to functionality a series of physiological approaches have been implemented that range from the flow-cytometric sorting of active intestinal bacteria and subsequent diversity analysis [5] to stable isotope probing of microbial communities that degrade specific sugars [6]. We also addressed the functionality of the intestinal microbiota by analysing its collective genome, termed microbiome, by applying a series of global approaches that exploit meta-proteomics and meta-transcrip-tomics [7]. Specific attention has been given to the functional micro-biomics of probiotic bacteria and their impact on related and other intestinal microbes. In these studies, Lactobacillus plantarum has been used a paradigm for host-microbe interactions as one of the first intestinal species for which the complete genome was determined. Advanced approaches focusing on the response of both the microbe and the host at the global transcriptional level allowed for deducing basic interaction mechanisms have been initiated that can be tested as comparative genomics and high throughput genetic tools have been well-established for L. plantarum [8–10].

Recent cited papers from the group include 1 Zoetendal EG, Vaughan EE, de Vos WM: A microbial world within us.

2 Egert M, de Graaf AA, Smidt H, de Vos WM, Venema K: Beyond diver-sity: Functional microbiomics of the human colon. Trends Microbiol 2006;14:86–91.

3 Rajilic´-Stojanovic´ M, Smidt H, de Vos WM: Diversity of the human gas-trointestinal tract microbiota revised. Environ Microbiol 2007; revised manuscript submitted.

4 Rajilic´-Stojanovic´ M: Diversity of the human gastrointestinal microbiota – Novel perspectives from high throughput analyses. 2007; Ph D Thesis Wageningen University, NL.

5 Ben-Amor KA, Heilig GHJ, Smidt H, Vaughan EE, Abee T, de Vos WM: Genetic diversity of viable, injured, and dead fecal bacteria assessed by fluorescence-activated cell sorting and 16S rRNA gene analysis. Appl Environ Microbiol 2005;71:4679–4689.

6 Egert M, de Graaf AA, Maathuis A, de Waard P, Plugge CM, Smidt H, Deutz NE, Dijkema C, de Vos WM, Venema K: Identification of glucose-fermenting bacteria present in an in vitro model of the human intestine by RNA-stable isotope probing. FEMS Microbiol Ecol 2007; February issue.

7 Klaassens ES, de Vos WM, Vaughan EE: A metaproteomics approach to study the functionality of the microbiota in the human infant gastrointes-tinal tract. Appl Environ Microbiol 2007;73:1388–1392.

8 Bron PA, Marco M, Hoffer SM, van Mullekom E, de Vos WM, Kleerebezem M: Genetic characterization of the bile salt response in

Lactobacillus plantarum and analysis of responsive promoters in vitro and

in situ in the gastrointestinal tract. J Bacteriol 2004;186:7829–35. 9 Sturme MHJ, Nakayama J, Molenaar D, Murakami Y, Kunugi R, Fujii T,

Vaughan EE, Kleerebezem M, de Vos WM: An agr-like two-component regulatory system in Lactobacillus plantarum is involved in production of a novel cyclic peptide and regulation of adherence. J Bacteriol 2005;187:5224–5235

10 Marco ML, Bongers RS, de Vos WM, Kleerebezem M: Spatial and temporal expression of Lactobacillus plantarum genes in the gastrointestinal tract of mice. Appl Environ Microbiol 2007;73:124–132.

S6-3 Gut Microbiomics and Nutrition

Gut microbiota and bioavailability of

food active microconstituents

Michael Blaut; Thomas Clavel German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

Lignans are phytoestrogens that are contained in a wide range of food items. Therefore, they are consumed daily in Western countries. They have been implicated in the prevention of breast and prostate cancer as well as athersosclerosis. However, they are extensively metabolized in the human body with subsequent changes in their biological properties. Lignans require activation by intestinal bacteria to exert estrogenic and antioxidant activities. We isolated and identi-fied several bacterial species involved in lignan activation and studied the catalytic steps leading from the plant lignan secoisolariciresinol diglucoside (SDG) to the bioactive lignans enterodiol (ED) and enterolacton (EL). The results indicate that the activation of SDG involves phylogenetically diverse bacteria, most of which are com-mon members of the dominant human intestinal microbiota.

S7-1 Nutrition and Cancers

Obesity and cancer. Results of the

EPIC study

E. Riboli

MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom Abstract not received.

S7-2 Nutrition and Cancers

Food factors, inflammation, biomarkers and

gastric cancer (the EurGast-EPIC study)

Gastric Cancer Epic Group

Unit of Nutrition, Environmental and Cancer, Catalan Institute of Oncology, Barcelona, Spain

Background: Dietary factors are thought to have an important role in gastric carcinogenesis, but evidence from cohort studies is lacking. We therefore investigated the risk of gastric cancer (GC) associated with meat and nitrosodimethylamine (NDMA) consump-tion, endogenous formation of nitroso compounds (ENOC), and their interaction with H. pylori (Hp) infection and plasma levels of vitamin C and other micronutrients.

Methods: 521,457 men and women aged 35–70 years partici-pated in the EPIC cohort in 10 European countries. Information regarding diet and lifestyle was collected at recruitment. Antibodies to Hp, vitamin C and other micronutrients plasma levels were mea-sured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. After an average of 6.5 years of follow-up, a total of 330 gastric were confirmed and classified by a panel of pathologists, and used for the analysis.

Results: There was a significant positive association between non-cardia GC and intakes of total, red, and processed meat (cali-brated HR  2.45; 95% 1.43–4.21 for an increase of 50 g/d). The association with total meat intake was strong in Hp infected subject, while no association was found in non-infected subjects. There was a significant positive association with ENOC and non-cardia cancer GC, with interactions between ENOC and Hp infection and plasma vitamin C levels. No association was found for NDMA intake. Dietary intake of antioxidants micronutrients were not associated with GC. However, higher plasma concentration of vitamin C, some carotenoids, retinol, and -tocopherol were associated with reduced risk of GC

Conclusion: Plasma levels of antioxidants were associated with reduced risk of GC, while total, red, processed meat intakes and ENOC were associated with an increased risk of non-cardia gastic cancer, especially in Hp infected subjects. Hp infection and vitamin C levels seem to modify the effect of dietary exposure.

S7-3 Nutrition and Cancers

Modulation of carcinogenesis by food

components: targets and mechanisms of

action

Beatrice L. Pool-Zobel; Nina Habermann;

Thomas Hofmann; Stefanie Klenow; Yvonne Knöbel; Claudia Miene; Umang Munjal; Daniel Scharlau; Selvaraju Veeriah; Michael Glei

Institute for Nutrition, Friedrich-Schiller University, Jena, Germany

Diet contributes to cancers of colon, breast and prostate by enhancing exposure to food-derived carcinogens and products of oxidative stress, which cause tumour initiation and progression. Protective ingredients may be chemoprotective by enhancing the metabolic detoxification of the risk factors which in the long run will reduce exposure. To study these associations, we are investigating how food ingredients modulate gene expression in human cells and how this affects the genotoxicity of selected risk factors. Extracts of foods are prepared. Non-soluble food ingredients (dietary fibres) are fermented in vitro to simulate conversions occurring in the gut lumen. Complex fermentation mixtures (e.g. containing butyrate, propionate, acetate), extracts (e.g. containing polyphenols) and corresponding individual compounds are incubated with human cells and responses are determined using c-DNA microarrays, real-time PCR, western blot, and functional assays for enzyme activities. The chemoprotec-tive consequences of the treatments are verified by determining the genotoxicity of selected genotoxins in cells treated with the putatively protective compound. The parameters may also be measured in bio-logical specimens (fecal water, peripheral lymphocytes, and cells from biopsies) from subjects receiving the functional food during dietary intervention trials. Mechanisms of protection in different human cells in vitro by butyrate, apple polyphenols or genistein include the enhanced expression of glutathione S-transferases (GSTs), an enzyme system with high detoxification capacity. The functional consequence of this induction are lower levels of DNA damage caused by genotoxic risk factors such as 4-hydroxynonenal, hydrogen peroxide and benzo(a)pyrene diolepoxide. If these effects occur in vivo in cells in which tumours arise they could present effective mechanisms of primary cancer prevention.

S8-1 Organ Sensing of Nutrients

Nutrient sensing in the brain

L. Pénicaud; A. Benani; A.L. Colombani; X. Fioramonti; T. Jaillard; C. Leloup; A. Lorsignol

UMR 5241 University Toulouse 3 – CNRS, Toulouse, France

Brain nutrient sensing allows a fine regulation of energy homeo-stasis through secretion of endocrine pancreatic hormones, regulation of liver glucose production, feeding behaviour and energy expendi-ture. Glucose sensing is the most studied. New insights into the cel-lular and molecular mechanism that support the fact that the electrical activity of some neurones depends on the glucose have been gained

recently. Making the analogy with the beta cell of the islet of Langerhans, it has been proposed that proteins such as glucose trans-porter 2, glucokinase and the ATP-dependent potassium channel, could assure this sensing. More recently the role of mitochondria and more specifically of recative oxygen species has been underlined.

Two types of glucosensing neurons had been characterized, those of which the activity is proportional to change in glucose concentra-tion and those of which the activity is inversely proporconcentra-tional to this change. It has been recently demonstrated that this was even more complex, since the response and the mechanism appear to be different in function of the level of the glucose change. Another important point is the demonstration that for some of the responses, the detec-tion is not probably at the level of the neuron itself but is insured by astrocyte indicating a coupling between the two types of cells. Finally numerous data have demonstrated the modulation of glucose sensing by other nutrients, in particular fatty acids as well as hormones (insu-lin, leptin and ghrelin) and peptides (NPY). The meaning of the recent observations is not clear yet but they indicate subtle mechanisms. This subtlety can be put in relation with different cellular and molec-ular mechanisms involved, thus explaining the discrepancies reported in the expression of different proteins (glucose transporters, hexoki-nases, channels). Astrocyte might be involved in one type of response thus adding a new level of complexity. Alteration in this sensing sys-tem could be at the origin of some alterations in feeding behaviour and glucose homeostasis leading to metabolic disorders.

S8-2 Organ Sensing of Nutrients

Amino-acids and skeletal muscle

University of Nottingham Medical School at Derby, Derby City General Hospital, Derby DE22 3DT, United Kingdom Of the common nutrients only amino acids have marked direct effects on human skeletal muscle protein turnover, and it is likely that these effects are confined to the essential amino acids and in particu-lar leucine. Amino acids show a dose related saturable effect on muscle protein synthesis (MPS) in the physiological range of amino acid availability, but one which appears to be time limited, with tac-hyphylaxis after ~3 h. The effects are confined to myofibrillar, sarco-plasmic and mitochondrial protein synthesis with no effects on muscle collagen synthesis.

The effects of amino acids on MPS are not mediated via stimula-tion of insulin secrestimula-tion and indeed appear to be independent of insulin action over a wide range of insulin availability. Rather, insulin seems to have a marked effect on the inhibition of protein breakdown, a mechanism likely unaffected by amino acid availability. Muscle shows appropriate alterations in the activity of signalling proteins of the PI3K-mTOR and MAPK pathways with increased availability of amino acids and insulin; as well as some novel regulatory amino-acid sensitive enzymes such as hvps34 and MAP4K3. Such signal integra-tion controls the characteristic effects of amino acids upon muscle protein metabolism.

In conditions of ageing, immobilisation, alcoholic cirrhosis and cancer cachexia we have evidence that muscle shows ‘anabolic resis-tance’ to amino acids, with a blunted response to their increased

availability. This phenomenon is likely caused by intracellular mecha-nisms involving a decreased sensitivity to amino acids in conditions of anabolic resistance, resulting in muscle wasting.

S8-3 Organ Sensing of Nutrients

Phytoestrogens and bone

Unité de Nutrition Humaine (UMR1019), Saint Genès-Champanelle, France

Phytoestrogens are a source for putative new and innovative dietary health intervention for postmenopausal women. They deserve special mention because emerging data support the hypothesis that these weakly oestrogenic compounds present in plants may represent a potential alternative therapy for a range of hormone-dependent conditions, a lower incidence of such diseases being associated with high intakes. Indeed, targeting bone health, in Asian countries, soy isoflavones consumption helps to prevent the demineralisation pro-cesses demonstrated in situations of estrogen deficiency and is associ-ated with a lower risk of fracture. Furthermore, lifestyle westernization induces loss of protection. However, conspicuous differences are encountered in Caucasian people, probably due to the very low aver-age intake. In such a population, supplementation studies investigat-ing bone turnover are not consistent. Nevertheless, substantial body of work has provided some evidence for significant improvement of bone mineral density after 6 months of supplementation. However recent studies carried out on longer term do not further confirm those potential promises. Anyway, because no clinical trial focussing on the effect of phytoestrogens on the risk of fracture (which is the ultimate hallmark for bone health) is available, a recommendation cannot be given at the current time. Moreover, before health professionals can actively advocate the increased consumption of soy, we need to gather more data on safety issues in order to rule out unknown metabolic effects with undesirable consequences.

S9-1 Food Properties affecting Food Intake

Appetite control and food intake

Institute of Psychological Sciences, University of Leeds, Leeds, UK

This system that controls appetite and food (energy) intake is complex and involves intimate interactions between physiology and behaviour. Appetite and satiety are two explanatory principles used to understand the control of energy intake. Unlike energy expenditure – which is part behaviour and part metabolism – energy intake is 100% behaviour. This behaviour is represented by the size and fre-quency of eating episodes along with the choice of foods; together these features make up the total energy consumed. These behavioural sequences are accompanied by subjective sensations such as hunger, fullness and urges to eat – which are sometimes regarded as the true

motivating drive to eat (or to stop eating). In an obesigenic environ-ment which constantly stimulates people to overconsume, what con-trols the feeling of fullness, and can the feeling be made to persist for longer? Is fullness simply the opposite of hunger? Why do some (most) people find it so difficult to exert control over the behaviour of eating? Is the tendency to overconsume brought about by the strength of the environment, or by psychobiological dispositions, or both?

The concept of the ‘Satiety Cascade’, first proposed 20 years ago (Blundell, Hill and Rogers, 1987), can be used to describe the pro-cesses that control appetite and to connect physiology with behaviour. The distinction between satiation (acts within a meal to control the termination of the eating episode) and satiety (acts in the pos-inges-tive period to inhibit further eating) is important.

The physiological signal is central to much theorizing on the con-trol of food intake. Consequently, it can be asked what are the major biological signals that influence the size and/or frequency of eating episodes, or the choice of foods? It is usual to distinguish 2 classes of physiological signals: tonic and episodic. Tonic signals are conceived to reflect activities arising from energy stores or tissue sites that exert a rather stable control over the drive for food. In contrast, episodic signals arise from periodic episodes of eating and exert temporary modulation over eating. The status of some signals is ambiguous since they appear to have a dual mode of operation. Signalling systems believed to control the amount of food eaten are normally considered separately from signals influencing the selection of foods; however, these systems certainly overlap.

A further distinction is the relative balance between pre-absorp-tive and post-absorppre-absorp-tive signals. Individuals vary in the strength of all of these signals.

A current important issue is the distinction between homeostatic and hedonic controls over food intake, and the extent to which each of these is responsible for overconsumption and weight gain. This can be thought of as the balance between hunger and pleasure. Both hun-ger and pleasure depend upon the ‘selection’ of particular foods, as well as from the intrinsic action of the foods themselves. Selection depends upon feelings of ‘liking’ and ‘wanting’ which are separate from the feeling of ‘hunger’ and ‘fullness’. Both selection and intrin-sic action influence satiation and/or satiety within the satiety cas-cade.

Our current understanding of the control of food consumption has reached a fascinating stage. There is considerable variability among people in their degree of control over appetite. A ‘weak satiety’ phe-notype can be considered. The identification of key characteristics of differences between people who readily overconsume and others who do not (susceptible and resistant individuals) can help to define the processes responsible for strengthening and prolonging the feeling of fullness.

http://www.psyc.leeds.ac.uk/cgi-bin/staff/index.pl?johneb Acknowledgment

John Blundell receives funding for research from the Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Council (MRC – Case), the European Commission (Frameworks 5 and 6) and from industrial partners in the nutrition and pharmaceutical sectors. John Blundell is also a paid consultant to industrial partners with an inter-est in the field of appetite control and obesity.

References

Barkeling B, King NA, Naslund E, Blundell JE: Characterisation of individu-als who claim to detect no relationship between their eating pattern and sensations of hunger and fullness. Int J Obesity. 2006.

Blundell JE, Finlayson GS: Is susceptibility to weight gain characterised by homeostatic or hedonic risk factors for over consumption? Physiology & Behaviour, 2004;82:21–25.

Blundell JE, Rogers PJ, Hill AJ: Evaluating the satiating power of foods: implications for acceptance and consumption. In: Solms J, Booth DA, Pangbourne RM, Raunhardt O (eds) Food Acceptance and Nutrition Academic Press, London 1987 pp 205–219.

Blundell JE, Stubbs RJ, Golding C, Croden FC, Alam R, Whybrow S, Lawton CL: Resistance and susceptibility to weight gain: Individual variability in response to a high fat diet. Physiol Behav, 2005;86:614–622.

Drapeau V, Blundell JE, Therrien F, Lawton CL, Richard D, Tremblay A: Appetite sensations as markers of overall intake. Br J Nutri, 2005;93:273– 280.

Drapeau V, King N., Hetherington M, Doucet E, Blundell J, Tremblay A: Appetite sensations and the satiety quotient: predictors of energy intake and weight loss. Appetite 2007;48:159–166.

Finlayson G, King N, Blundell J: Is it possible to dissociate ‘liking’ and ‘want-ing’ for foods in humans? A novel experimental procedure. Physiol Behav 2007;90:36–42.

S9-2 Food Properties affecting Food Intake

Meals, snacks and energy balance

Division of Human Nutrition and Epidemiology, Wageningen University, The Netherlands Abstract not received.

S9-3 Food Properties affecting Food Intake

Role of fibre in satiety and hormonal

responses

Karhunen Leila

Mediteknia, University of Kuopio, Finland

Dietary fibre can increase the satiety value of food, both within and between the meals. Due to the distinct physical and chemical properties of different fibres, time course and mechanisms mediating satiety effects may differ between fibres. The effects are, however, particularly related to the bulking or viscosity-producing properties of fibres and distributed along the gastrointestinal tract. The requirement for mechanical processing is usually greater after fibre-rich food, which enhances the amount of satiety signals arising from the mouth and other parts of the gastrointestinal tract. Fibre also decreases energy density, and quite often, the palatability of the food, which also promotes satiety. Increased fibre amount has also been linked to the decreased rate of gastric emptying and the decreased rate of macro-nutrient absorption. Fibre-stimulated colonic fermentation has also received attention as a potential factor inducing fibre-related satiety, although this remains speculative.

So far, only a limited number of studies have investigated the effects of dietary fibres on gastrointestinal satiety-related hormones, such as cholecystokinin, glucagon-like peptide 1 or peptide YY. Based on the current knowledge, dietary fibres modify the gastroin-testinal hormonal responses and both augmented and attenuated responses have been reported. However, the results have been quite inconsistent and seem to vary according to the type and amount of fibre used. Also other elements, such as food structure, might modify the responses. More studies are therefore needed to understand which properties and postprandial profiles are most favourable for the sati-ety-producing effects of various dietary fibres.

S10-1 Nutrients & Adipose Tissue

Omega 6 fatty acids and excessive adipose

tissue development

Gérard Ailhaud

CNRS UMR 6543, Centre de Biochimie, Faculté des Sciences, Nice, France

During adipogenesis, long-chain fatty acids act at the preadipocyte stage and stimulate the formation of adipocytes. Fatty acids as well as eicosanoïds, i.e. prostaglandins and leukotrienes arising from arachi-donic acid (ARA) metabolism, behave as activators/ligands of PPAR / and PPAR. In vitro, ARA plays an additional role as a precursor of prostacyclin which then activates the PKA pathway through the cell surface prostacyclin receptor IP-R. Under isoenergetic conditions, in vivo experiments have shown that i) a LA-enriched diet enhances fat mass and -linolenic acid (LNA) counteracts this effect and ii) a critical role is played byARA and the prostacyclin receptor in excessive adi-pose tissue development during the gestation/lactation period. Thus PUFAs of the n-6 and n-3 series are NOT equipotent in promoting adi-pogenesis in vitro and adipose tissue development in vivo. Changes over the last decades in the fatty acid composition of fats observed in breast milk, formula milk and most foods, i.e. a high increase in LA with slight or no change in LNA content, may be responsible at least in part of the dramatic rise in the prevalence of childhood overweight and obesity. Whether prevention of obesity appears as a key issue for pres-ent and future generations, the status of dietary lipids should be recon-sidered from the very beginning of the food chain.

S10-2 Nutrients & Adipose Tissue

Food constituents and quantity as

determinants of differentiation of adipose

progenitor cells

Jan Nedergaard; Natasa Petrovic; James A. Timmons; Barbara Cannon

The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, Stockholm, Sweden

To identify the qualitative differences between the progenitors of white and brown adipocytes, we have performed microarray analysis