Emerging evidence suggests that dietary phytochemicals, in particular flavonoids, may exert beneficial effects on the central nervous system by protecting neurons against stress-induced injury, by suppressing neuroinflammation and by improving cognitive function. It is likely that flavonoids exert such effects, through selective actions on different components of a number of protein kinase and lipid kinase signalling cascades, such as the phosphatidylinositol-3 kinase (PI3K)/Akt, protein kinase C and mitogen-activated protein kinase (MAPK) pathways. This review explores the potential inhibitory or stimulatory actions of flavonoids within these pathways, and describes how such interactions are likely to underlie neurological effects through their ability to affect the activation state of target molecules and/or by modulating gene expression. Future research directions are outlined in relation to the precise site(s) of action of flavonoids within signalling pathways and the sequence of events that allow them to regulate neuronal function.

We previously reported that in rats, long-term Zn deficiency significantly reduced taste sensitivity and total carbonic anhydrase (CA) activity in the submandibular gland. We therefore investigated the effects of Zn deficiency on salivary secretion and the expressions of CA isozymes (II and VI) in the rat submandibular gland, since those isozymes are thought to be related to taste sensation and salivary secretion. Male Sprague–Dawley rats, age 4 weeks, were divided into three groups (Zn-def, low-Zn and pair-fed, that were fed a diet containing 2·2, 4·1 or 33·7 mg Zn/kg, respectively, for 42 d). Northern blot analysis indicated that Zn deficiency reduced CA II mRNA expression in the submandibular gland without reducing CA VI mRNA expression. In Western blot analysis, Zn deficiency significantly reduced CA II (erythrocyte CA) protein expression in the submandibular gland without reducing CA VI protein expression. Salivary secretion was lower in the Zn-def group than in the pair-fed group. These results suggest that decreased CA isozyme II expression underlies the decreased CA activity previously reported in the submandibular gland in Zn-def rats, and this may reduce regular salivary secretion.

Recent recommendations by the American Diabetes Association suggest that children with type 1 diabetes should follow the recommendations for age, sex and body size of the general population. In the case of being overweight or obese, weight-control strategies should be applied. Adherence to recommendations should be pursued by continuous nutritional education that should start at the onset of diabetes and maintained by means of nutritional counselling to the family. The second main target of nutritional intervention is to encourage a reproducible daily meal plan that can be maintained by acquiring good habits when making nutritional choices. Finally, children and parents should be taught how to count carbohydrates, which would help them manage exceptions in their daily meal plan. Specifically, nutritional recommendations for children with diabetes focus on limiting the intake of foods of animal origin (red meat, cheese, cold cuts), moderating fat intake and promoting the intake of foods that naturally contain fibre (mainly vegetables, legumes, fruit). There are two at-risk periods in the lives of children when nutritional education procedures as well as diabetes care in general are less likely to be effective: early years of life and adolescence. In the case of very young children, new behavioural-based intervention strategies to help parents improve mealtimes could be useful in teaching diabetic children to learn to follow a structured eating schedule, which is desirable for long-lasting efficacy in diabetes care. In adolescents, eating disorders and insulin misuse for weight control purposes are concrete and difficult problems to deal with. A good balance between eating for pleasure and maintaining one's health is a challenge for anyone. Appropriate nutritional education helps children with diabetes to find this balance and enjoy a better quality of life.

The objective of this study was to evaluate potential anti-atherogenic properties of hen eggs enriched naturally with conjugated linoleic acid (CLA) isomers (cis-9, trans-11 and trans-10, cis-12). Eighteen apoE and LDL receptor double-knockout mice (apoE/LDLR− / − ), at the age of 4 months with pre-established atherosclerosis, were randomly assigned to three experimental groups (n 6) and fed AIN-93G-based diets for the next 2 months. The experimental diets were: AIN-93G+ CLA-free egg-yolk powder (control); AIN-93G+ CLA-free egg-yolk powder +0·1 % CLA (CLA-supplemented eggs); and AIN-93G+ CLA-enriched egg-yolk powder, providing 0·1 % CLA (CLA-enriched eggs). For assessment of anti-atherogenic properties of CLA-enriched or CLA-supplemented eggs the following criteria were used: (1) serum lipid profile; (2) development of atherosclerosis; and (3) composition of atherosclerotic plaque. CLA-enriched eggs, compared with CLA-supplemented eggs, reduced significantly (P < 0·05) total plasma cholesterol in the mice. At the same time, both CLA-supplemented eggs and CLA-enriched eggs tended to decrease the size of atherosclerotic plaque in aortic roots of mice. Most importantly, atherosclerotic plaques of mice fed CLA-enriched eggs showed significantly (P < 0·05) reduced number of atherogenic macrophages and increased area occupied by smooth muscle cells in atherosclerotic lesions. In conclusion, CLA-enriched eggs exerted an anti-inflammatory effect more effectively than CLA-supplemented eggs. This anti-inflammatory effect can be considered their major functional claim that warrants further exploitation.

Dietary Reference Intake (DRI) values exist for vitamins and minerals, and provide a guideline on the optimal dose range to avoid deficiency and prevent toxicity. Polyphenols are widely distributed in plant foods, and have been linked to improved human health through reduced risk of chronic diseases, especially cardiovascular. Although they do not cause classical deficiencies, recently they have been discussed as ‘lifespan essentials because they are needed to achieve a full lifespan by reducing the risk of a range of chronic diseases. A recent meta analysis shows promising actions of polyphenols from cocoa, soya and tea on flow mediated dilation, blood pressure and LDL cholesterol. Many epidemiological studies support the action of polyphenols or polyphenol-rich foods on health, but there are still many gaps in our knowledge. More adequately powered, randomised, placebo controlled human studies are needed on polyphenols. There is a large number of structurally different polyphenols which are relevant for health, and obtaining enough information to set a DRI for each of these will not be feasible in the foreseeable future. A new approach is needed, and a new way of thinking, which would apply not only to polyphenols but also to other phytochemicals. Today, a target intake value of polyphenols as ‘lifespan essentials’ needs to be based on the amount of polyphenols in ‘5-a-day’. We are heading in the right direction towards a DRI, but bioavailability and dose-effects, including toxic levels, need to be established before DRIs can be considered.

Epidemiological evidence together with preclinical data from animal and in vitro studies strongly support a correlation between soy isoflavone consumption and protection towards breast and prostate cancers. The biological processes modulated by isoflavones, and especially by genistein, have been extensively studied, yet without leading to a clear understanding of the cellular and molecular mechanisms of action involved. This review discusses the existing gaps in our knowledge and evaluates the potential of the new nutrigenomic approaches to improve the study of the molecular effects of isoflavones. Several issues need to be taken into account for the proper interpretation of the results already published for isoflavones. Too often knowledge on isoflavone bioavailability is not taken into account; supra-physiological doses are frequently used. Characterization of the individual variability as defined by the gut microflora composition and gene polymorphisms may also help to explain the discrepancies observed so far in the clinical studies. Finally, the complex inter-relations existing between tissues and cell types as well as cross-talks between metabolic and signalling pathways have been insufficiently considered. By appraising critically the abundant literature with these considerations in mind, the mechanisms of action that are the more likely to play a role in the preventive effects of isoflavones towards breast and prostate cancers are reviewed. Furthermore, the new perspectives opened by the use of genetic, transcriptomic, proteomic and metabolomic approaches are highlighted.

Recent data reported that inulin-type fructans extracted from chicory roots regulate appetite and lipid/glucose metabolism, namely, by promoting glucagon-like peptide-1 (GLP-1) production in the colon. The Agave genus growing in different regions of Mexico also contains important amounts of original fructans, with interesting nutritional and technological properties, but only few data report their physiological effect when added in the diet. Therefore, we decided to evaluate in parallel the effect of supplementation with 10 % agave or chicory fructans on glucose and lipid metabolism in mice. Male C57Bl/6J mice were fed a standard (STD) diet or diet supplemented with Raftilose P95 (RAF), fructans from Agave tequilana Gto. (TEQ) or fructans from Dasylirion spp. (DAS) for 5 weeks. The body weight gain and food intake in mice fed fructans-containing diets were significantly lower than the ones of mice fed the STD diet, TEQ leading to the lowest value. Serum glucose and cholesterol were similarly lower in all fructans-fed groups than in the STD group and correlated to body weight gain. Only RAF led to a significant decrease in serum TAG. As previously shown for RAF, the supplementation with agave fructans (TEQ and DAS) induced a higher concentration of GLP-1 and its precursor, proglucagon mRNA, in the different colonic segments, thus suggesting that fermentable fructans from different botanical origin and chemical structure are able to promote the production of satietogenic/incretin peptides in the lower part of the gut, with promising effects on glucose metabolism, body weight and fat mass development.

Methionine is an essential amino acid and methyl donor for most transmethylation reactions in mammals. The product of transmethylation reactions is homocysteine, which is associated with enhanced risk for CVD. The aim of this study was to analyse metabolic and vascular functional consequences of a methionine-enriched diet in rats. The dose of methionine was chosen to reflect the range of over-nutrition in man. We quantified plasma levels of homocysteine, asymmetrical dimethylarginine and adenosine, determined methionine and its metabolites in tissues and blood plasma and assessed relaxation of mesenteric arteries toward acetylcholine and sodium nitroprusside. A methionine-enriched diet for 4 weeks elevated homocysteine levels in plasma 2-fold and in spleen by 70 %. The level of S-adenosylhomocysteine was increased in liver only, while methionine and S-adenosylmethionine were unchanged in all organs studied. Plasma adenosine and asymmetrical dimethylarginine levels were unchanged, as were vessel relaxations. A 2-fold elevation of plasma homocysteine, which is assigned a risk indicator for cardiovascular events, did not impair mesenteric artery vasodilatation during 4 weeks of a methionine-rich diet. Furthermore, asymmetrical dimethylarginine and adenosine, which have been shown to be changed in more severe degrees of hyperhomocysteinaemia, remained unaltered.

The present study was to test the relative hypercholesterolaemic and atherogenic potency of oxidised cholesterol (OxC) and non-oxidised cholesterol in hamsters. An OxC mixture, prepared by heating pure cholesterol (100 g) at 160°C in air for 72 h, contained 78 % cholesterol and 22 % OxC. Fifty Golden Syrian hamsters were randomly divided into five groups of ten animals and fed the control diet, a 0·05 % cholesterol diet (C-0·05), a 0·10 % cholesterol diet (C-0·1), a 0·05 % OxC mixture diet (OxC-0·05) or a 0·10 % OxC mixture diet (OxC-0·1), respectively. The OxC-0·05 and OxC-0·1 groups were more hypercholesterolaemic and had serum total cholesterol 22 and 12 % higher than the corresponding C-0·05 and C-0·1 hamsters (P < 0·05). The OxC-0·1 group demonstrated greater deposition of cholesterol and had a larger area of atherosclerotic plaque in the aorta than the corresponding C-0·1 hamsters (P < 0·05). Similarly, the aorta in the OxC-0·1 group showed greater inhibition on acetylcholine-induced relaxation compared with that in the C-0·1 hamsters. It was concluded that OxC was much more hypercholesterolaemic and atherogenic than cholesterol.

This study investigated the effects of β-carotene and canthaxanthin on lipid peroxidation and antioxidative enzyme activities in rats fed a high-cholesterol, high-fat diet. Wistar rats were divided into six groups. Negative control group (group NC) received a high-fat (150 g/kg) diet; cholesterol control group (group CC) received a high-cholesterol (10 g/kg), high-fat diet. The other four groups were fed a high-cholesterol, high-fat diet supplemented with crystal β-carotene (group BC), β-carotene beadlet (group BB), canthaxanthin beadlet (group CX) or α-tocopherol (group AT). Blood and livers were collected for analysis after 6 weeks of feeding. Group BB had significantly lower hepatic thiobarbituric acid reactive substance (TBARS) and conjugated diene concentrations, whereas group CX had a significantly lower plasma TBARS concentration than did group CC. In erythrocytes, glutathione peroxidase activities were significantly greater in groups BC, BB and CX than in group CC. Moreover, compared with group CC, catalase activities were significantly greater in groups BB and CX, and superoxide dismutase (SOD) activity was significantly greater in group BB. In livers, SOD activities were significantly greater in groups BC, BB and CX, and glutathione reductase activities were significantly greater in groups BB and CX than in group CC. Compared with group CC, hepatic retinol and α-tocopherol concentrations were significantly greater in groups BC, BB and CX, whereas plasma and hepatic cholesterol concentrations were significantly lower in group BC. These findings suggest that β-carotene and canthaxanthin altered the pro-oxidation and antioxidation balance and suppressed cholesterol-induced oxidative stress via modulation of antioxidant system and cholesterol metabolism.

The international symposium organised by the Danone Institute as a pre-congress satellite of the European Nutrition Societies Congress, in Paris, in July 2007, brought together experts of child nutrition and behaviour. These experts coming from several countries of Europe and North America shared their views on the impact of numerous factors affecting child eating and health in present-day developed societies. Topics included nutritional influences during foetal life, early life development of food likes and dislikes, neophobia, ability for energy regulation, impact of media and advertisement, etc. Most contributions addressed the obesity epidemics and the problems associated with body weight control. Other aspects of child health were also considered, for example the nutritional challenge of adequately feeding children with type 1 diabetes. The nine speakers were asked to underline practical strategies to improve nutrition in early life, so as to maximise health, growth and quality of life in today's environment. The present paper is a summary of the ideas expressed by the experts, highlighting agreements, convergences, and occasional disagreements between expert opinions.

The aim of the present study was to elucidate the mechanism of the vitamin B12 deficiency-induced changes of the serine dehydratase (SDH) and tyrosine aminotransferase (TAT) activities in the rat liver. When rats were maintained on a vitamin B12-deficient diet, the activities of these two enzymes in the liver were significantly reduced compared with those in the B12-sufficient control rats (SDH 2·8 (sd 0·56) v. 17·5 (sd 6·22) nmol/mg protein per min (n 5); P < 0·05) (TAT 25·2 (sd 5·22) v. 41·3 (sd 8·11) nmol/mg protein per min (n 5); P < 0·05). In the B12-deficient rats, the level of SDH induction in response to the administration of glucagon and dexamethasone was significantly lower than in the B12-sufficient controls. Dexamethasone induced a significant increase in TAT activity in the primary culture of the hepatocytes prepared from the deficient rats, as well as in the cells from the control rats. However, a further increase in TAT activity was not observed in the hepatocytes from the deficient rats, in contrast to the cells from the controls, when glucagon was added simultaneously with dexamethasone. The glucagon-stimulated production of cAMP was significantly reduced in the hepatocytes from the deficient rats relative to the cells from the control rats. Furthermore, the glucagon-stimulated adenylyl cyclase activity in the liver was significantly lower in the deficient rats than in the controls. These results suggest that vitamin B12 deficiency results in decreases in SDH and TAT activities correlated with the impairment of the glucagon signal transduction through the activation of the adenylyl cyclase system in the liver.

Oxidation of LDL is hypothesised as an early and critical event in atherogenesis. Oxidised LDL (oxLDL) favour the transformation of macrophages into foam cells, an important cell involved in atherosclerosis. Furthermore, oxLDL cause multiple changes in macrophage functions. Thus, oxLDL induces certain genes, suppresses others and alters cell lipid metabolism. Consumption of a Mediterranean diet is associated with a low incidence of atherosclerotic disease, but data about the specific dietary constituents involved and mechanisms conferring cardioprotection are still sparse. The aim of the present study was to determine the effect of representative minor components of wine and olive oil on reactive oxygen species and eicosanoid synthesis induced by oxLDL-stimulated macrophages. We observed that exposure to non-toxic oxLDL concentrations leads to the production of H2O2 by RAW 264.7 macrophages and this effect was reverted by apocynin, a NADPH oxidase inhibitor. Moreover, oxLDL induced arachidonic acid (AA) release, cyclo-oxygenase-2 overexpression and subsequent PGE2 release. We observed that resveratrol and tyrosol revert H2O2 production induced by oxLDL as well as AA release and PGE2 synthesis and that these effects were not as a consequence of these compounds interfering with the oxLDL binding to their receptors. Interestingly, β-sitosterol presence enhances these polyphenol actions. Thus, we found a synergistic action of polyphenols of olive oil and wine and β-sitosterol of olive oil led to the modulation of the effects of oxLDL on oxidative stress and PGE2 synthesis.

As in man, canine obesity is associated with insulin resistance, dyslipidaemia and other chronic diseases. This study was designed to examine the effects of a nutritional supplement (green tea) on insulin sensitivity and plasma lipid concentrations in an obese insulin-resistant dog model. We also determined mRNA expression of two transcription factors, PPARγ and PPARα, and some of their target genes, including GLUT4, lipoprotein lipase (LPL) and adiponectin. Obese dogs were divided into two groups: a green tea group (n 6); a control group (n 4). Dogs in the green tea group were given green tea extract (80 mg/kg per d) orally, just before their single daily meal, for 12 weeks. Insulin sensitivity (using a euglycaemic–hyperinsulinaemic clamp) and concentrations of plasma TAG, total cholesterol and NEFA were assessed in each group. Gene expression was measured in visceral and subcutaneous adipose tissues and in liver and skeletal muscle, by real-time PCR. At 12 weeks in the green tea group, mean insulin sensitivity index was 60 (sem 11) % higher (P < 0·05) and TAG concentration 50 (sem 10) % lower (P < 0·001), than baseline. PPARγ, GLUT4, LPL and adiponectin expression were significantly higher in both adipose tissues, whilst PPARα and LPL expression were significantly higher in skeletal muscle, compared with baseline. These findings show that nutritional doses of green tea extract may improve insulin sensitivity and lipid profile and alter the expression of genes involved in glucose and lipid homeostasis.

This review examines the extent to which transcriptomic methods have lived up to their promise in the context of nutrition research, placing particular emphasis on examples from micronutrient research. A case is made that the high quality platform technologies now available, together with established standards and systems for data storage and exchange and powerful new methods of data analysis, mean that microarrays have reached a level of technical maturity at which they can be exploited to their full potential. In the context of nutrition and micronutrient research, transcriptomic methods have already been widely applied, albeit primarily in studies using cell lines and animal models. Using this type of approach, a multitude of genes regulated at the mRNA level by dietary components has been identified and this, in turn, has provided new insights into the biological processes affected by nutritional parameters. Evidence from the very limited number of published transcriptomics-based nutritional studies performed in human volunteers suggests that, with appropriate study design, it is feasible to apply transcriptomic methods successfully in dietary intervention trials. On the other hand, gene expression-based biomarker development still poses a major challenge. Here the use of expression profile ‘signatures’, rather than single genes, may provide a solution. Approaches designed to identify such ‘signatures’ are being developed and tested widely, primarily in the context of medical research. The applicability and power of such approaches should also be evaluated in the context of nutrition.

Dietary phytochemicals, of which polyphenols form a considerable part, may affect the risk of obesity-associated chronic diseases such as type 2 diabetes. This article presents an overview on how phytochemicals, especially polyphenols in fruits, vegetables, berries, beverages and herbal medicines, may modify imbalanced lipid and glucose homeostasis thereby reducing the risk of the metabolic syndrome and type 2 diabetes complications.

In subjects with untreated type 2 diabetes, we previously determined that a weight-maintenance, non-ketogenic diet containing 30 % protein, 50 % fat and 20 % carbohydrate (30:50:20) decreased the percentage total glycohaemoglobin (%tGHb) by 2·2 % glycohaemoglobin over 5 weeks compared to a diet recommended for the American public (protein–fat–carbohydrate 15:30:55). Both the fasting and postprandial glucose were decreased. The objective of the present study was to determine if increasing the carbohydrate content from 20 to 30 % at the expense of fat would still provide a similar effect on %tGHb, fasting and postprandial glucose concentration. Eight men with untreated type 2 diabetes were studied over a 5-week period. Results at the beginning (standard diet) and end of the 5-week study were analysed. Body weight was stable. Fasting glucose concentration decreased by 40 %; 24 h glucose area response decreased by 45 %. Insulin did not change. Mean %tGHb decreased by 1·7 (from 10·8 to 9·1 %), and was still decreasing linearly at 5 weeks. In conclusion, a high-protein, 30 % carbohydrate diet could be a patient-empowering method of improving the hyperglycaemia of type 2 diabetes without pharmacologic intervention. Long-term effects and general applicability of this diet remain to be determined.

Asian plantain (Plantago asiatica) essential oil (PAEO) contains multiple bioactive compounds, but its potential effects on lipid metabolism have not been examined. PAEO was found to be mostly composed of oxygenated monoterpenes, with linalool as the major component (82·5 %, w/w), measured using GC–MS. Incubation of 0–200 μg PAEO/ml with HepG2 cells for 24 h resulted in no significant toxicity. Incubation with 0·2 mg PAEO/ml altered the expression of LDL receptor (+83 %; P < 0·05) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase ( − 37 %; P < 0·05), as assessed using RT-PCR. LDL oxidation was markedly inhibited by PAEO treatment due to the prevalence of linalool compounds in PAEO. Oral administration of PAEO for 3 weeks in C57BL/6 mice significantly reduced plasma total cholesterol and TAG concentrations by 29 and 46 %, respectively. The mRNA (+58 %; P < 0·05), but not protein, levels of the LDL receptor were significantly higher, whereas both mRNA and protein levels of HMG-CoA reductase were significantly lower ( − 46 and − 11 %, respectively; P < 0·05) in the liver of PAEO-fed than of control mice. The mRNA levels of CYP7A1 were marginally reduced in HepG2 cells, but not in mouse liver after PAEO treatment. Thus, PAEO may have hypocholesterolaemic effects by altering the expression of HMG-CoA reductase. Reduced TAG and oxidised LDL may provide additional cardiovascular protective benefits.

The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (–F) or in three key methyl donors, folic acid, choline and methionine (–FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism, energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both –F and –FLMLC diets. The mRNA for PPARα and PPARγ and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the –FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the –F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the –FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.

Biotin is a member of the vitamin B-complex family. Biotin deficiency has been associated with hyperglycaemia and insulin resistance in animals and humans. In the present study, we investigated the pharmacological effects of biotin on hypertension in the stroke-prone spontaneously hypertensive rat (SHRSP) strain. We observed that long-term administration of biotin decreased systolic blood pressure in the SHRSP strain; also, a single dose of biotin immediately decreased systolic blood pressure in this strain. Pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazole [4,3-α]quinoxalin-1-one abolished the hypotensive action of biotin in the SHRSP strain, while pretreatment with the NO synthase inhibitor NG-nitro-l-arginine methyl ester had no effect on the action of biotin. Biotin reduced coronary arterial thickening and the incidence of stroke in the SHRSP strain. These results suggest that the pharmacological dose of biotin decreased the blood pressure of the SHRSP via an NO-independent direct activation of soluble guanylate cyclase. Our findings reveal the beneficial effects of biotin on hypertension and the incidence of stroke.