Dietary patterns have been related to health outcomes and morbi-mortality. Mediterranean diet indexes are correlated with adequate nutrient intake. The objective of the present study was to analyse the adequacy of nutrient intake of a posteriori defined Mediterranean (MDP) and Western (WDP) diet patterns in the Seguimiento Universidad de Navarra (SUN) cohort. A sample of 17 197 subjects participated in the study. Participants completed a 136-item validated semi-quantitative FFQ. Principal component analysis was used to define dietary patterns. Individuals were classified according to quintiles of adherence based on dietary pattern scores. Non-dietary variables, such as smoking and physical activity habits, were also taken into account. The probability approach was used to assess nutrient intake adequacy of certain vitamins (vitamins B12, B6, B3, B2, B1, A, C, D and E) and minerals (Na, Zn, iodine, Se, folic acid, P, Mg, K, Fe and Ca). Logistic regression analysis was used to assess the adequacy of nutrient intake according to adherence to dietary patterns. WDP and MDP were defined. A higher quintile of adherence to an MDP was associated to a lower prevalence of inadequacy for the intake of Zn, iodine, vitamin E, Mg, Fe, vitamin B1, vitamin A, Se, vitamin C and folic acid. The adjusted OR for not reaching at least six (or at least ten) nutrient recommendations were 0·09 (95 % CI: 0·07, 0·11) (and 0·02 (95 % CI: 0·00, 0·16)) for the upper quintile of MDP and 4·4 (95 % CI: 3·6, 5·5) and 2·5 (95 % CI: 1·1, 5·4) for the WDP. The MDP was associated to a better profile of nutrient intake.

SCFA are produced in the gut by bacterial fermentation of undigested carbohydrates. Activation of the Gαi-protein-coupled receptor GPR41 by SCFA in β-cells and sympathetic ganglia inhibits insulin secretion and increases sympathetic outflow, respectively. A possible role in stimulating leptin secretion by adipocytes is disputed. In the present study, we investigated energy balance and glucose homoeostasis in GPR41 knockout mice fed on a standard low-fat or a high-fat diet. When fed on the low-fat diet, body fat mass was raised and glucose tolerance was impaired in male but not female knockout mice compared to wild-type mice. Soleus muscle and heart weights were reduced in the male mice, but total body lean mass was unchanged. When fed on the high-fat diet, body fat mass was raised in male but not female GPR41 knockout mice, but by no more in the males than when they were fed on the low-fat diet. Body lean mass and energy expenditure were reduced in male mice but not in female knockout mice. These results suggest that the absence of GPR41 increases body fat content in male mice. Gut-derived SCFA may raise energy expenditure and help to protect against obesity by activating GPR41.

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

The effects of an exogenous enzyme preparation, the application method and feed type on ruminal fermentation and microbial protein synthesis were investigated using the rumen simulation technique (Rusitec). Steam-rolled barley grain and chopped alfalfa hay were sprayed with water (control, C), an enzyme preparation with a predominant xylanase activity (EF), or autoclaved enzyme (AEF) 24 h prior to feeding, or the enzyme was supplied in the buffer infused into the Rusitec (EI). Microbial N incorporation was measured using (15NH4)2SO4 in the buffer. Spent feed bags were pummelled mechanically in buffer to segregate the feed particle-associated (FPA) and feed particle-bound (FPB) bacterial fractions. Enzymes applied to feed reduced neutral-detergent fibre content, and increased the concentration of reducing sugars in barley grain, but not alfalfa hay. Ruminal cellulolytic bacteria were more numerous with EF than with C. Disappearance of DM from barley grain was higher with EF than with C, but alfalfa was unaffected by EF. Treatment EF increased incorporation of 15N into FPA and FPB fractions at 24 and 48 h. In contrast, AEF reduced the 24 h values, relative to C; AEF and C were similar at 48 h. Infused enzyme (EI) did not affect 15N incorporation. Xylanase activity in effluent was increased by EF and EI, compared to C, but not by AEF. Xylanase activity in FPA was higher at 48 h than at 24 h with all treatments; it was higher with EF than C at 24 and 48 h, but was not altered by AEF or EI. Applying enzymes onto feeds before feeding was more effective than dosing directly into the artificial rumen for increasing ruminal fibrolytic activity.

Trends in global fish catches are described together with fish landlings and fish consumption in the UK. The importance of n–6 and n–3 polyunsaturated fatty acids as essential constituents of human diets is considered and the role of oily fish as a dietary source of the long-chain n–3 polyunsaturates, docosahexaenoic acid and eicosapentaenoic acid, is emphasized. The origin ofn–3 polyunsaturates in the marine phytoplankton and their transmission via zooplankton to fish is described as a means of understanding the consumption of different fish body oils. The ease with which the fatty acid composition of fish body oils can be manipulated by altering the fatty acid composition of their feeds is emphasized and the dietary requirements of marine and freshwater fish for n–3 and n–6 polyunsaturates considered. Farming fish on diets containing principally fish meal and fish oil, as used in salmon production in Scotland, generates a high quality product with levels of long-chain n–3 polyunsaturates equalling or exceeding those of wild fish. Farming fish on high quality marine oils rich in docosahexaenoic and eicosapentaenoic acids is an efficient means of delivering these essential nutrients in human diets and also efficiently exploiting a strictly limited marine bioresource.

Brown seaweeds such as Ascophyllum nodosum are a rich source of phlorotannins (oligomers and polymers of phloroglucinol units), a class of polyphenols that are unique to Phaeophyceae. At present, there is no information on the bioavailability of seaweed polyphenols and limited evidence on their bioactivity in vivo. Consequently, we investigated the gastrointestinal modifications in vitro of seaweed phlorotannins from A. nodosum and their bioavailability and effect on inflammatory markers in healthy participants. In vitro, some phlorotannin oligomers were identified after digestion and colonic fermentation. In addition, seven metabolites corresponding to in vitro-absorbed metabolites were identified. Urine and plasma samples contained a variety of metabolites attributed to both unconjugated and conjugated metabolites (glucuronides and/or sulphates). In both urine and plasma, the majority of the metabolites were found in samples collected at late time points (6–24 h), suggesting colonic metabolism of high-molecular-weight phlorotannins, with three phlorotannin oligomers (hydroxytrifuhalol A, 7-hydroxyeckol, C-O-C dimer of phloroglucinol) identified in urine samples. A significant increase of the cytokine IL-8 was also observed. Our study shows for the first time that seaweed phlorotannins are metabolised and absorbed, predominantly in the large intestine, and there is a large inter-individual variation in their metabolic profile. Three phlorotannin oligomers present in the capsule are excreted in urine. Our study is the first investigation of the metabolism and bioavailability of seaweed phlorotannins and the role of colonic biotransformation. In addition, IL-8 is a possible target for phlorotannin bioactivity.

The changes in metabolic efficiency, body composition, and nutrient partitioning induced by high-fat feeding were evaluated in adult rats (90d of age). The alterations in serum free triiodothyronine, insulin, and leptin levels, as well as in hepatic and skeletal muscle metabolism, were also assessed. Rats were fed either a low- or a high-fat diet for 2 weeks. Relative to the low-fat feeding, energy intake and expenditure, as well as body-energy gain, lipid gain, and energetic efficiency, were increased by the high-fat feeding. Increased serum leptin levels accompanied these variations. A positive correlation between serum leptin levels and percentage of body fat was found in the rats fed the low- or high-fat diet, with a significant divergence between the slope of the regression lines. Furthermore, a negative correlation between serum leptin level and energy intake was found in the rats fed the low-fat diet, while a positive correlation was found in the rats fed the high-fat diet. Finally, the high-fat feeding decreased the hepatic and skeletal muscle mitochondrial oxidative capacity. It is concluded that, in adult rats, a nutritional factor such as a high level of fat in the diet induces obesity, leptin resistance, and impairment of mitochondrial capacity, all phenomena typical of unrestrained aged rats.

Resveratrol, a polyphenol abundantly found in grapes and red wine, exhibits beneficial health effects due to its anti-inflammatory properties. In the present study, we evaluated the effect of resveratrol on inflammatory responses induced by lipopolysaccharide (LPS) treatment of human intestinal Caco-2 and SW480 cell lines. In the LPS-treated intestinal cells, resveratrol dose-dependently inhibited the expression of inducible NO synthase (iNOS) mRNA as well as protein expression, resulting in a decreased production of NO. In addition, Toll-like receptor-4 expression was significantly diminished in LPS-stimulated cells after resveratrol pre-treatment. To investigate the mechanisms by which resveratrol reduces NO production and iNOS expression, we examined the activation of inhibitor of κB (IκB) in LPS-stimulated intestinal cells. Results demonstrated that resveratrol inhibited the phosphorylation, as well as the degradation, of the IκB complex. Overall, these results show that resveratrol is able to reduce LPS-induced inflammatory responses by intestinal cells, interfering with the activation of NF-κB-dependent molecular mechanisms.

The long-term physiological effects of refined carbohydrates on appetite and mood remain unclear. Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake, mood and BMI in normal-weight women (n 133). Subjects were categorised as ‘watchers’ or ‘non-watchers’ of what they ate then received sucrose or artificially sweetened drinks (4 × 250 ml per d). Expectancies were varied by labelling drinks ‘sugar’ or ‘diet’ in a counter-balanced design. Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales. By 4 weeks, sucrose supplements significantly reduced total carbohydrate intake (F(1,129) = 53·81; P < 0·001), fat (F(2,250) = 33·33; P < 0·001) and protein intake (F(2,250) = 28·04; P < 0·001) compared with sweetener supplements. Mean daily energy intake increased by just under 1000 kJ compared with baseline (t (67 df) = 3·82; P < 0·001) and was associated with a non-significant trend for those receiving sucrose to gain weight. There were no effects on appetite or mood. Neither dietary restraint status as measured by the Dutch Eating Behaviour Questionnaire nor the expectancy procedure had effects. Expectancies influenced mood only during baseline week. It is concluded that sucrose satiates, rather than stimulates, appetite or negative mood in normal-weight subjects.

The effectiveness of a health and nutrition education programme, in changing certain chronic disease risk factors, was assessed after the 6 years intervention period was completed. The school-based intervention programme was applied to all children registered in the first grade (age 5·5–6·5 years) in 1992 in two counties of Crete, while the children from a third county served as a control group. In order to assess the effectiveness of the intervention, a variety of biological and behavioural parameters were measured before and following completion of the intervention in a randomly selected school-based sample of 602 intervention group (IG) and 444 control group (CG) pupils. At the end of the 6-year period, it was found that biochemical indices generally improved significantly more in the IG compared with the CG (mean change for IG v. CG was -0·27 v. -0·12 mmol/l for total cholesterol (TC); -0·07 v. +0·24 for TC:HDL and -0·13 v. +0·14 for LDL:HDL). Similarly, the changes observed in the anthropometric variables in the two groups were in favour of the IG (+3·68 v. +4·28 kg/m2 for BMI; +2·97 v. +4·47 mm for biceps skinfold). Total energy intake and consumption of total fat and saturated fat increased significantly less in the IG compared with the CG (+747·7 v. 1534·7 kJ (+178·7 v. +366·8 kcal); +5·9 v. +18·8 g and +0·8 v. +5·1 g respectively), while time devoted to leisure time physical activity and cardiovascular run test performance increased significantly more in the IG (+281 v. +174 min/week and +2·5 v. +1·2 stages respectively). The findings of the present study underline the importance of such programmes in health promotion and disease prevention. Although the long-term effects of these programmes can only be assessed by tracking this population through to adolescence and adulthood, these programmes seem to have the potential to lead to a healthier lifestyle and thus a reduction in risk factor levels.

In the present study we evaluate the blood pressure-lowering effect of the following products: the hydrolysate obtained from egg white (EW) by enzymatic treatment with pepsin (HEW), the peptide fraction of HEW with molecular mass lower than 3000 Da (HEW<3000 Da), and three peptide sequences isolated from HEW<3000 Da (Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu: YAEERYPIL); (Arg-Ala-Asp-His-Pro-Phe-Leu: RADHPFL); and (Ile-Val-Phe (IVF)). These peptides, and also HEW and HEW<3000 Da, had been characterized previously in vitro as potent inhibitors of angiotensin-converting enzyme (ACE). EW and the products mentioned earlier were orally administered by gastric intubation, to 17–20-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats. We measured the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats by the tail cuff method before administration and also 2, 4, 6, 8 and 24h post-administration. Distilled water served as negative control, and we used captopril (50mg/kg) as positive control to carry out similar experiments with a known ACE inhibitor. HEW, HEW<3000 Da and the three peptide sequences decreased SBP and DBP in SHR but they did not modify these variables in WKY rats. The peptide sequences YAEERYPIL, RADHPFL and IVF showed a potency to decrease blood pressure greater than HEW or HEW<3000 Da. The results obtained suggest that the studied products could be used as a functional food with potential therapeutic benefit in the prevention and treatment of hypertension.

To determine the influence of masticatory efficiency on postprandial satiety and glycaemic response, twenty-one healthy males were recruited for this randomised cross-over trial. The participants consumed a fixed amount of pizza provided in equal-sized portions by chewing each portion either fifteen or forty times before swallowing. Subjective appetite was measured by appetite questionnaires at regular intervals for 3 h after the meal and plasma samples were collected for the measurement of selected satiety-related hormones, glucose, insulin and glucose-dependent insulinotropic peptide (GIP) concentrations. An ad libitum meal was provided shortly after the last blood sample was drawn and the amount eaten recorded. Compared with fifteen chews, chewing forty times per portion resulted in lower hunger (P= 0·009), preoccupation with food (P= 0·005) and desire to eat (P= 0·002). Meanwhile, plasma concentrations of glucose (P= 0·024), insulin (P< 0·001) and GIP (P< 0·001) were higher following the forty-chews meal. Chewing forty times before swallowing also resulted in a higher plasma cholecystokinin concentration (P= 0·045) and a trend towards a lower ghrelin concentration (P= 0·051). However, food intake at the subsequent test meal did not differ (P= 0·851). The results suggest that a higher number of masticatory cycles before swallowing may provide beneficial effects on satiety and facilitate glucose absorption.

The slow digestible disaccharide isomaltulose (iso; Palatinose™) is available as novel functional carbohydrate ingredient for manufacturing of low glycaemic foods and beverages. Although basically characterised, various information on physiological effects of iso are still lacking. Thus, the objective of the present study was to expand scientific knowledge of physiological characteristics of iso by a set of three human intervention trials. Using an ileostomy model, iso was found to be essentially absorbed, irrespective of the nature of food (beverage and solid food). Apparent digestibility of 50 g iso from two different meals was 95·5 and 98·8 %; apparent absorption was 93·6 and 96·1 %, respectively. In healthy volunteers, a single dose intake of iso resulted in lower postprandial blood glucose and insulin responses than did sucrose (suc), while showing prolonged blood glucose delivery over 3 h test. In a 4-week trial with hyperlipidaemic individuals, regular consumption of 50 g/d iso within a Western-type diet was well tolerated and did not affect blood lipids. Fasting blood glucose and insulin resistance were lower after the 4-week iso intervention compared with baseline. This would be consistent with possible beneficial metabolic effects as a consequence of the lower and prolonged glycaemic response and lower insulinaemic burden. However, there was no significant difference at 4 weeks after iso compared with suc. In conclusion, the study shows that iso is completely available from the small intestine, irrespective of food matrix, leading to a prolonged delivery of blood glucose. Regular iso consumption is well tolerated also in subjects with increased risk for vascular diseases.

The relationship between total body water (TBW) and extracellular water (ECW), measured by deuterium oxide dilution and bromide dilution respectively, and impedance and impedance index (height2/impedance) at 1, 5, 50 and 100 kHz was studied. After correction for TBW, ECW was correlated only with the impedance index at 1 and 5 kHz. After correction for ECW, TBW was best correlated with the impedance index at 100 kHz. The correlation of body-water compartments with impedance values obtained with modelling programs was lower than with measured impedance values. Prediction formulas for ECW (at 1 and 5 kHz) and TBW (at 50 and 100 kHz) were developed. The prediction errors for ECW and TBW were 1·0 and 1·7 kg respectively (coefficient of variation 5%). The residuals of both ECW and TBW were related to the ECW/TBW value. Application of the prediction formulas in a population, independently measured, revealed a slight overestimation of TBW and ECW, which could be largely explained by differences in the validation group in body-water distribution and in body builds. The ratio of impedance at 1 kHz to impedance at 100 kHz was correlated with body-water distribution (ECW/TBW). The relation is however not strong enough to be useful as a predictor. It is concluded that an independent prediction of ECW and TBW, using impedance at low and high frequency respectively, is possible, but that the bias depends on the body-water distribution and body build of the measured subject.

Four pigs fitted with a gastric cannula were fed on a wheat-flour-based diet (WF) and three oat-based diets, consisting mainly of oat flour (OF), rolled oats (RO) or oat bran (OB), for 1 week each. The stomach contents were collected quantitatively daily at 0·5, 1, 2, 3 or 5 h after feeding. The viscosity (mPa. s) of the liquid fraction of stomach contents 1 h after feeding was 1·7 with diet WF, 15 with diet OF, 30 with diet RO and approximately 400 with diet OB. The viscosity and the concentration of β-glucan in the liquid phase was to some extent determined by the dietary level of β-glucan in the diet. However, there was a trend towards a lower viscosity after longer exposure to the gastric juices. The correlation between logarithmic values for viscosity and concentration of β-glucan in the liquid phase of digesta was r 0·45. On centrifugation of digesta there was a higher proportion present in the sediment phase when the pigs were fed on diets with a higher content of soluble dietary fibre (DF), suggesting that the digesta was more coherent. This possibility was supported by the higher water-holding capacity (WHC) of the sediment. Feeding diets with oats containing a higher soluble DF content led to lower recoveries of digesta, PEG 4000 (liquid-phase marker), and the DF components β-glucan and arabinoxylan in the first hour after feeding. No effect related to the DF content of the diet was seen in the gastric emptying of starch and Cr2O3 (solid-phase marker). In conclusion, soluble DF from oatsincreased the viscosity of stomach contents and increased the ability of the dry matter to retain water. Higher levels of soluble DF led to higher recoveries of digesta, the liquid phase and DF itself in the initial stage of gastric emptying, whereas no effect was seen on the gastric emptying of starch.

Gangliosides are acid glycosphingolipids widely distributed in most vertebrate tissues and fluids. They are present in mammalian milk, where they are almost exclusively associated with the membrane fraction of the fat globule. In human milk, the content and individual distribution of gangliosides changes during lactation, GD3 being the most abundant ganglioside in colostrum, while in mature milk, GM3 is the major individual species. Gangliosides function as “unintended” target receptors for bacterial adhesion in specific tissues. After oral administration, they can be putative decoys that interfere with pathogenic binding in the intestine, this being the main mechanism by which these compounds can prevent infection. Ganglioside-supplemented infant formula has been reported to modify the intestinal ecology of preterm newborns, increasing the Bifidobacteria content and lowering that of Escherichia coli. In addition, the influence of dietary gangliosides on several parameters related to the development of intestinal immune system, such as cytokine and intestinal IgA production, has also been described in animal models. Recently, the influence of GM3 and GD3 on dendritic cell maturation and effector functionalities has also been reported, suggesting a role for these milk gangliosides, especially GD3, in modulating the process of oral tolerance during first stages of life. In summary, dietary gangliosides may have an important role in the modification of intestinal microflora and the promotion of intestinal immunity development in the neonate, and consequently in the prevention of infections during early infancy.

In many cells throughout the body, vitamin D is converted into its active form calcitriol and binds to the vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D-metabolising enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating the effects of vitamin D. Preclinical and epidemiological studies have provided evidence for anti-cancer effects of vitamin D (particularly against colorectal cancer), although clinical trials have yet to prove its benefit. In addition, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene–environment interaction analyses and clinical trials on vitamin D efficacy in colorectal cancer patients. In this study, we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies and discuss the links and controversies within and between the two parts of evidence.

1. A study of ammonia and urea metabolism in sheep was made using isotope dilution techniques with (15NH4)2SO4, [15N]urea and [14C]urea in order to determine quantitatively the movements of urea-N and NH3-N throughout the body of normal, feeding sheep.

2. Single injections of 15N-labelled compounds were made into the rumen fluid NH3, caecal fluid NH3 and the blood urea pools, in order to estimate the rates of flux through, and the transfer of N between, these and other nitrogenous pools in the body. 51Cr EDTA was injected into the rumen and caecum with (15NH4)2SO4 to allow estimation of fluid volumes and to provide an indication of mixing, and of times of transit of isotopes between different sampling sites in the digestive tract.

3. The sheep ate approximately 22 g lucerne chaff/h and the mean dietary N intake was 16.3 g/d.

4. The rate of flux of NH3 through the rumen NH3 pool was 15.0 g/d (i.e. 90% of the dietary N ingested; however, this amount also included N from plasma urea (1.1 g/d) and other endogenous sources including NH3 derived from caecal NH3 (0.4 g/d).

5. Only 40% of the N in isolated rumen bacteria was derived from NH3, indicating that a considerable proportion of their N requirements were obtained from compounds other than NH3 (e.g. peptides and amino acids).

6. There was evidence of recycling of N between nitrogenous pools in the rumen, probably through rumen NH3 → microbial N → NH3.

7. It was estimated that 5.3 g blood urea-N/d entered the digestive tract: 20% of this urea was degraded in the rumen, 25% in the caecum and the remainder was apparently degraded elsewhere; there was evidence of urea degradation in the large intestine posterior to the caecum and it is suggested that urea degradation and absorption of the resultant NH3 may occur in the ileum.

8. Of the 4.8 g N/d entering the caecal NH3 pool, 4.2 g N/d left and did not return and the difference (0.6 g N/d) was recycled, possibly through caecal NH3 → microbial N → NH3.

9. A large proportion of the NH3 entering the caecal NH3 pool (70% or 3.2 g N/d) was apparently derived from degradation of nitrogenous products, other than urea, including rumen microbial N (1.0 g N/d) passing undigested from the small intestine.

10. Less than half the NH3-N of caecal origin entering the rumen passed through the blood urea pool; the remainder was apparently transported as other nitrogenous compounds in the blood or body fluids.

11. The results of the three experiments were combined in a general three-pool, opencompartment model which formally recognizes an unlimited number of other unspecified, interconnected pools together comprising the whole-animal system. Rates of flux through, and transfer of N between these and other nitrogenous pools in the body were calculated by solving this model and the information derived has been applied to whole-animal models with a view to subsequently using these models in computer simulation studies.

The worldwide increase in the incidence of obesity is a consequence of a positive energy balance, with energy intake exceeding expenditure. The signalling systems that underlie appetite control are complex, and the present review highlights our current understanding of key components of these systems. The pattern of eating in obesity ranges from over-eating associated with binge-eating disorder to the absence of binge-eating. The present review also examines evidence of defects in signalling that differentiate these sub-types. The signalling network underlying hunger, satiety and metabolic status includes the hormonal signals leptin and insulin from energy stores, and cholecystokinin, glucagon-like peptide-1, ghrelin and peptide YY3-36 from the gastrointestinal tract, as well as neuronal influences via the vagus nerve from the digestive tract. This information is routed to specific nuclei of the hypothalamus and brain stem, such as the arcuate nucleus and the solitary tract nucleus respectively, which in turn activate distinct neuronal networks. Of the numerous neuropeptides in the brain, neuropeptide Y, agouti gene-related peptide and orexin stimulate appetite, while melanocortins and α-melanocortin-stimulating hormone are involved in satiety. Of the many gastrointestinal peptides, ghrelin is the only appetite-stimulating hormone, whereas cholecystokinin, glucagon-like peptide-1 and peptide YY3-36 promote satiety. Adipose tissue provides signals about energy storage levels to the brain through leptin, adiponectin and resistin. Binge-eating has been related to a dysfunction in the ghrelin signalling system. Moreover, changes in gastric capacity are observed, and as gastric capacity is increased, so satiety signals arising from gastric and post-gastric cues are reduced. Understanding the host of neuropeptides and peptide hormones through which hunger and satiety operate should lead to novel therapeutic approaches for obesity; potential therapeutic strategies are highlighted.

Although the inverse association between coffee consumption and risk of diabetes has been reported numerous times, the role of caffeine intake in this association has remained unclear. We evaluated the consumption of coffee and other beverages and food containing caffeine in relation to the incidence of diabetes. The study participants were 5897 men and 7643 women in a community-based cohort in Takayama, Japan. Consumption of coffee, green tea, oolong tea, black tea and chocolate snacks were measured with a semi-quantitative FFQ in 1992. At the follow-up survey in 2002, the development of diabetes and the time of diagnosis were reported. To assess the association, age, smoking status, BMI, physical activity, education in years, alcohol consumption, total energy intake, fat intake and women's menopausal status were adjusted. Among men who consumed one cup per month to six cups per week and among those who consumed one cup per d or more, the associated hazard ratios were 0·69 (95 % CI 0·50, 0·97) and 0·69 (95 % CI 0·49, 0·98) compared with those who drank little to no coffee, with a P value for trend of 0·32. The hazard ratios for women with the same coffee consumption patterns were 1·08 (95 % CI 0·74, 1·60) and 0·70 (95 % CI 0·44, 1·12), with a P value for trend of 0·03. The association between estimated total caffeine intake and risk of diabetes was insignificant both among men and among women. The results imply that coffee consumption decreased the risk of developing diabetes. The protective effect may exist aside from the influence of caffeine intake.