The present study investigates the effects of genotype on responses to alternative feeds in Atlantic salmon. Microarray analysis of the liver transcriptome of two family groups, lean or fat, fed a diet containing either a fish oil (FO) or a vegetable oil (VO) blend indicated that pathways of cholesterol and lipoprotein metabolism might be differentially affected by the diet depending on the genetic background of the fish, and this was further investigated by real-time quantitative PCR, plasma and lipoprotein biochemical analysis. Results indicate a reduction in VLDL and LDL levels, with no changes in HDL, when FO is replaced by VO in the lean family group, whereas in fat fish fed FO, levels of apoB-containing lipoproteins were low and comparable with those fed VO in both family groups. Significantly lower levels of plasma TAG and LDL-TAG were measured in the fat group that was independent of diet, whereas plasma cholesterol was significantly higher in fish fed the FO diet in both groups. Hepatic expression of genes involved in cholesterol homeostasis, β-oxidation and lipoprotein metabolism showed relatively subtle changes. A significantly lower expression of genes considered anti-atherogenic in mammals (ATP-binding cassette transporter A1, apoAI, scavenger receptor class B type 1, lipoprotein lipase (LPL)b (TC67836) and LPLc (TC84899)) was found in lean fish, compared with fat fish, when fed VO. Furthermore, the lean family group appeared to show a greater response to diet composition in the cholesterol biosynthesis pathway, mediated by sterol-responsive element-binding protein 2. Finally, the presence of three different transcripts for LPL, with differential patterns of nutritional regulation, was demonstrated.

Recent studies have suggested that chito-oligosaccharides can have anti-adipogenic properties. The objectives of the present study were to evaluate the anti-adipogenic potential of four different chito-oligosaccharides (molecular weight (MW) < 1000, 1000–3000, 3000–5000 and 5000–10 000 Da) and to identify molecular mechanisms underlying the chito-oligosaccharide-mediated inhibition of adipogenesis. Mouse 3T3-L1 cells were allowed to differentiate in the presence of chito-oligosaccharide. At day 8 post-induction of differentiation, lipid accumulation, free glycerol release and the quantitative expression of adipogenic marker genes were evaluated. Chito-oligosaccharides had concentration- and MW-dependent inhibitory effects on lipid accumulation (P < 0·001 and < 0·05, respectively), as well as a concentration-dependent effect (P < 0·001) on free glycerol release and the expression of adipogenic marker genes. The 5000–10 000 Da chito-oligosaccharide was selected for subsequent molecular studies. A panel of forty-four lipid metabolic pathway-specific genes was analysed by quantitative real-time PCR. Chito-oligosaccharide-mediated inhibition of adipogenesis was associated with the up-regulation of the IL-6 gene at all concentrations of chito-oligosaccharide examined and the PG-endoperoxide synthase 2 (PTGS2) gene at higher concentrations of chito-oligosaccharide. The effect of chito-oligosaccharide on gene expression was validated by measuring IL-6 protein concentrations in the media. Finally, an IL-6 promoter assay was developed to characterise the effect of chito-oligosaccharide on the transcriptional activity of the IL-6 promoter, which was increased in a concentration-dependent manner (P < 0·001). We conclude that IL-6 is a candidate signalling molecule in the chito-oligosaccharide-mediated inhibition of adipogenesis in 3T3-L1 cells.

Observational studies have indicated that soya food consumption is inversely associated with blood pressure (BP). Evidence from randomised controlled trials (RCT) on the BP-lowering effects of soya protein intake is inconclusive. We aimed to evaluate the effectiveness of soya protein intake in lowering BP. The PubMed database was searched for published RCT in the English language through to April 2010, which compared a soya protein diet with a control diet. We conducted a random-effects meta-analysis to examine the effects of soya protein on BP. Subgroup and meta-regression analyses were performed to explore possible explanations for heterogeneity among trials. Meta-analyses of twenty-seven RCT showed a mean decrease of 2·21 mmHg (95 % CI − 4·10, − 0·33; P = 0·021) for systolic BP (SBP) and 1·44 mmHg (95 % CI − 2·56, − 0·31; P = 0·012) for diastolic BP (DBP), comparing the participants in the soya protein group with those in the control group. Soya protein consumption significantly reduced SBP and DBP in both hypertensive and normotensive subjects, and the reductions were markedly greater in hypertensive subjects. Significant and greater BP reductions were also observed in trials using carbohydrate, but not milk products, as the control diet. Meta-regression analyses further revealed a significantly inverse association between pre-treatment BP and the level of BP reductions. In conclusion, soya protein intake, compared with a control diet, significantly reduces both SBP and DBP, but the BP reductions are related to pre-treatment BP levels of subjects and the type of control diet used as comparison.

In order to study whether lipid metabolism may be affected by maximum replacement of dietary fish oil and fish meal with vegetable oils (VO) and plant proteins (PP), Atlantic salmon (Salmo salar L.) smolts were fed a control diet containing fish oil and fish meal or one of three plant-based diets through the seawater production phase for 12 months. Diets were formulated to meet all known nutrient requirements. The whole-body lipid storage pattern was measured after 12 months, as well as post-absorptive plasma, VLDL and liver TAG. To further understand the effects on lipid metabolism, expression of genes encoding for proteins involved in VLDL assembly (apoB100), fatty acid uptake (FATP1, cd36, LPL and FABP3, FABP10 and FABP11) were measured in liver and visceral adipose tissue. Maximum dietary VO and PP increased visceral lipid stores, liver TAG, and plasma VLDL and TAG concentrations. Increased plasma TAG correlated with an increased expression of apoB100, indicating increased VLDL assembly in the liver of fish fed the high-plant protein- and VO-based diet. Atlantic salmon fed intermediate replacement levels of VO or PP did not have increased body fat or visceral mass. Overall, the present results demonstrate an interaction between dietary lipids and protein on lipid metabolism, increasing overall adiposity and TAG in the body when fish meal and fish oil are replaced concomitantly at maximised levels of VO and PP.

There is substantial evidence to link what we eat to the reduction of the risk of major chronic diseases and/or the improvement of functions. Thus, it is important for public health agencies and the food industry to facilitate the consumption of foods with particular health benefits by providing consumer products and messages based on scientific evidence. Although fragmentary advice is available from a range of sources, there is a lack of comprehensive scientific guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods. Such guidelines are needed both to support nutrition science in general, and to facilitate the substantiation of health claims. In the present study, which presents the consensus view of an International Life Sciences Institute Europe Expert Group that included senior scientists from academia and industry, the term ‘foods’ refers to foods, dietary supplements and food constituents, but not to whole diets. The present study is based on an initial survey of published papers, which identified the range and strengths and weaknesses of current methodologies, and was finalised following exchanges between representatives from industry, academia and regulatory bodies. The major factors involved in the design, conduct and reporting of studies are identified, summarised in a checklist table that is based on the Consolidated Standards of Reporting Trials guidelines, and elaborated and discussed in the text.

Although the number of iodine-deficient countries has been reduced by almost 50 % over the last decade, it still remains a frequently misunderstood health problem. The most devastating effects of iodine deficiency occur during fetal development and childhood, periods in which sufficient iodine delivery remains critical. Besides the determination of thyroid size, the concentration of urinary iodine, serum thyroid-stimulating hormone and serum thyroglobulin are useful biomarkers to assess iodine status. Severe iodine deficiency is associated with neurological complications, cretinism, endemic goitre development, hypothyroidism, decreased fertility and increased infant mortality. The recommended iodine supplementation strategies are based on correction of iodine deficiency, close monitoring and evaluation of iodine administration, cooperation of the salt industry, training of local health care professionals and education of the population. Besides the multiple beneficial effects of supplementation, we present in this review a critical look at the possible side effects.

The usual treatment for phenylketonuria (PKU) is a phenylalanine-restricted diet. Following this diet is challenging, and long-term adherence (and hence metabolic control) is commonly poor. Patients with PKU (usually, but not exclusively, with a relatively mild form of the disorder) who are responsive to treatment with pharmacological doses of tetrahydrobiopterin (BH4) have either lower concentrations of blood phenylalanine or improved dietary phenylalanine tolerance. The availability of a registered formulation of BH4 (sapropterin dihydrochloride, Kuvan®) has raised many practical issues and new questions in the dietary management of these patients. Initially, patients and carers must understand clearly the likely benefits (and limitations) of sapropterin therapy. A minority of patients who respond to sapropterin are able to discontinue the phenylalanine-restricted diet completely, while others are able to relax the diet to some extent. Care is required when altering the phenylalanine-restricted diet, as this may have unintended nutritional consequences and must be undertaken with caution. New clinical protocols are required for managing any dietary change while maintaining control of blood phenylalanine, ensuring adequate nutrition and preventing nutritional deficiencies, overweight or obesity. An accurate initial evaluation of pre-sapropterin phenylalanine tolerance is essential, and the desired outcome from treatment with sapropterin (e.g. reduction in blood phenylalanine or relaxation in diet) must also be understood by the patient and carers from the outset. Continuing education and support will be required thereafter, with further adjustment of diet and sapropterin dosage as a young patient grows.

The increase in the prevalence of obesity in recent years has prompted research into alternative methods of modulating body weight and body fat. The last decade has reflected this with a surge in studies investigating the potential of green tea as a natural agent of weight loss, with a view to confirming and elucidating the mechanisms underlying its effect on the body. Currently, it is widely believed that the polyphenolic components present in green tea have an anti-obesogenic effect on fat homeostasis, by increasing thermogenesis or reducing fat absorption among other ways. The data published to date, however, are inconsistent, with numerous putative modes of action suggested therein. While several unimodal mechanisms have been postulated, a more plausible explanation of the observed results might involve a multimodal approach. Such a mechanism is suggested here, involving simultaneous inhibition of the enzymes catechol-O-methyltransferase, acetyl-CoA carboxylase, fatty acid synthase and impeding absorption of fat via the gut. An evaluation of the available evidence supports a role of green tea in weight loss; however the extent of the effects obtained is still subject to debate, and requires more objective quantification in future research.

The palliative treatment of patients with advanced pancreatic cancer (APC) has undergone little advancement in the last 15 years. Novel therapies that have been investigated to extend survival have shown little benefit over existing chemotherapy regimens. Patients with APC often experience significant weight loss, which is one of the primary factors involved in declining quality of life. Recently, the ability of n-3 fatty acid rich oral preparations to attenuate or reverse tumour-related weight loss has been investigated in this patient group with encouraging results. Laboratory investigation has also yielded promising results suggesting a potential direct tumouricidal effect of n-3 fatty acids as well as the putative potentiation of existing chemotherapy regimes. The present review aims to examine the potential applications of fish oils rich in n-3 fatty acids in patients with APC, present a selection of the studies carried out to date and outline avenues of possible further clinical investigation.

Fish oils, rich in long-chain n-3 PUFA, are known to reduce various risk factors for CVD. However, conclusive evidence regarding the benefits of n-3 on arterial stiffness, a risk factor for CVD, has not yet been established. Consequently, we conducted the first study aimed to quantify the effects of n-3 supplementation on arterial stiffness through meta-analysis. Multiple databases and clinical trial registries were systematically searched up until September 2010 for randomised and controlled adult human clinical trials to investigate the effects of long-chain n-3 fatty acids on arterial stiffness. No limits were set on dosage sizes or sample characteristics. A total of ten n-3 trials met the final inclusion criteria; four using pulse wave velocity (PWV) and six using arterial compliance, measured as capacitive compliance or systemic arterial compliance, as respective outcome measures. Meta-analysis revealed that n-3 was statistically significant in effectively improving both PWV (g = 0·33; 95 % CI 0·12, 0·56; P < 0·01) and arterial compliance (g = 0·48; 95 % CI 0·24, 0·72; P < 0·001). There was no evidence of heterogeneity or publication bias. Results were not influenced by changes in blood pressure, heart rate or BMI. The findings of the present study reveal that supplementation with n-3 offers a scientifically supported means of reducing arterial stiffness. Reduction in arterial stiffness by n-3 may account for some of its purported cardioprotective effects.

Non-steroidal anti-inflammatory drugs cause gastric ulceration through a number of mechanisms including inhibition of PG synthesis, generation of reactive oxygen species (ROS) and induction of apoptosis. Recently, matrix metalloproteinases (MMP) have been suggested to play a crucial role in these mechanisms. The present study investigated the protective effect of anthocyanins isolated from black rice bran (Heugjinjubyeo) against naproxen-induced gastric mucosal injury in rats. The oral administration of anthocyanins (5, 25 or 50 mg/kg body weight) showed significant protection against naproxen (80 mg/kg body weight)-induced gastric ulcer and inhibited lipid peroxidation in the gastric mucosa. In addition, pretreatment with anthocyanins resulted in a significant increase in the activities of radical-scavenging enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Also biochemical and zymographic analyses suggested that the administration of anthocyanins gives a significant protection against naproxen-induced gastric antral ulcer through scavenging ROS and regulation of matrix metalloproteinase-2 (MMP-2) activity. The results of intracellular radical activation show that anthocyanins suppress the generation of intracellular ROS and attenuate the suppression of MMP-2 activity by naproxen. These results suggest that anthocyanins extracted from black rice may offer potential remedy of gastric antral ulceration.

The physiological relevance of oestradiol (E2) on post-orchiectomy (OX) food intake control was evaluated in six adult, male, domestic, short-hair cats. Jugular venous plasma E2 and oestrone (E1) concentrations were determined weekly before OX and immediately after OX in a cross-over trial of two 3-week periods in which E2 (0·5 μg) or vehicle (0·1 ml/kg) was subcutaneously injected daily and blood was sampled 4 h later. Plasma E1 and E2 concentrations before OX were 32 (se 8·3) and 4·3 (se 1·0) pg/ml, respectively. Following OX, plasma concentrations of E2 were decreased (P = 0·04) while those of E1 were unchanged. Injections of E2 increased (P = 0·02) plasma E2 towards pre-OX concentrations. In a second cross-over trial, plasma E1 and E2 were determined weekly during the last 3 weeks of two 8-week periods in which food was continuously presented or restricted to 110 % of pre-OX amounts. Continuous food presentation compared with restricted food presentation resulted in greater body weight (6·4 (se 0·4) v. 5·4 (se 0·4) kg, P = 0·02) and body fat percentage (29 (se 3) v. 23 (se 2) %, P = 0·09) but no significant changes were observed in plasma E1 and E2 concentrations. Hence, circulating E2 appears to be reduced by OX, while it is not significantly changed by body-fat gain. The amount of E2 injected after OX was not supraphysiological; it restored plasma E2 to pre-OX concentrations and reduced food intake in five of the six cats by a mean of 14 (se 3) %.

Lactate is increasingly recognised to be more than a simple end product of anaerobic glycolysis. Skeletal muscle and white adipose tissue are considered to be the main sites of lactate production and release. Recent studies have demonstrated that there is a specific G-protein coupled receptor for lactate, GPR81, which is expressed primarily in adipose tissue, and also in muscle. Lactate inhibits lipolysis in adipose tissue by mediating, through GPR81, the anti-lipolytic action of insulin. A high proportion (50 % or more) of the glucose utilised by white adipose tissue is converted to lactate and lactate production by the tissue increases markedly in obesity; this is likely to reflect a switch towards anaerobic metabolism with the development of hypoxia in the tissue. During exercise, there is a shift in fuel utilisation by muscle from lipid to carbohydrate, but this does not appear to be a result of the inhibition of lipolysis in the main adipose tissue depots by muscle-derived lactate. It is suggested instead that a putative autocrine lactate loop in myocytes may regulate fuel utilisation by muscle during exercise, operating via a muscle GPR81 receptor. In addition to being an important substrate, lactate is a key signal in metabolic regulation.

Treatment with a combination of four nutrients, i.e. R-α-lipoic acid, acetyl-l-carnitine, nicotinamide and biotin, just as with pioglitazone, significantly improves glucose tolerance, insulin release, plasma NEFA, skeletal muscle mitochondrial biogenesis and oxidative stress in Goto–Kakizaki (GK) rats. However, it is not known whether treatment with these nutrients can improve mitochondrial function and reduce oxidative stress in GK rats. The effects of a combination of these four nutrients on mitochondrial function, oxidative stress and apoptosis in GK rat liver were investigated. Livers of untreated GK rats showed (1) abnormal changes in the activities of mitochondrial complexes (decreases in I, III and IV and increases in II and V), (2) increases in protein oxidation, (3) decreases in antioxidant enzymes (superoxide dismutase, glutathione S-transferase, NADH-quinone oxidoreductase-1), (4) a decrease in total antioxidant capacity but increases in reduced glutathione level and glyceraldehyde 3-phosphate dehydrogenase expression and (5) significant increases in apoptosis biomarkers, including expression of p21 and p53. A 3-month treatment with the four nutrients significantly improved most of these abnormalities in GK rats, and the effects of the nutrient combination were greater than those of pioglitazone for most of these indices. These results suggest that dietary supplementation with nutrients that are thought to influence mitochondrial function may be an effective strategy for improving liver dysfunction in GK diabetic rats.

Starch is the major energy source for monogastric mammals and humans. The present study was conducted to evaluate the liver metabolic responses of weaned pigs fed with different dietary starches. A total of sixteen weaned pigs were fed with two experimental diets containing either cassava starch (CS, 80 % amylopectin and 20 % amylose) or maize starch (70 % amylopectin and 30 % amylose). The present results showed that the growth performance was not affected by different dietary starches (P>0·05). However, ingestion of CS not only increased the lipid content in liver tissues, but also elevated the concentrations of serum cholesterol and insulin (P < 0·05). The metabolic responses induced by CS were associated with more lipogenic enzymes such as fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase in liver (P < 0·05). Real-time PCR quantification for lipid metabolic genes indicated that ingestion of CS not only up-regulated the expression of these lipogenic genes, but also decreased the expression of lipolytic genes. These results suggested that the metabolic responses of weaned pigs fed with different dietary starches may vary widely depending on their composition, and ingestion of starches that are high in amylopectin may produce a stronger insulinaemic response and lead to an up-regulation of lipogenesis in the liver.

The objective of the present review is to highlight the relationship between low vitamin B6 status and CVD through its link with inflammation. While overt vitamin B6 deficiency is uncommon in clinical practice, increasing evidence suggests that marginal vitamin B6 deficiency is rather frequent in a consistent proportion of the population and is related to an increased risk of inflammation-related diseases. Ample evidence substantiates the theory of atherosclerosis as an inflammatory disease, and low plasma vitamin B6 concentrations have been related to increased CVD risk. Several studies have also shown that low vitamin B6 status is associated with rheumatoid arthritis and chronic inflammatory bowel diseases, both of which hold an underlying chronic inflammatory condition. Furthermore, the inverse association observed between inflammation markers and vitamin B6 supports the notion that inflammation may represent the common link between low vitamin B6 status and CVD risk. In addition to the epidemiological evidence, there are a number of cell culture and animal studies that have suggested several possible mechanisms relating impaired vitamin B6 status with chronic inflammation. A mild vitamin B6 deficiency characterises, in most cases, a subclinical at-risk condition in inflammatory-linked diseases which should be addressed by an appropriate individually tailored nutritional preventive or therapeutic strategy.

While it has been proposed, based on epidemiological studies, that whole grains may be beneficial in weight regulation, possibly due to effects on satiety, there is limited direct interventional evidence confirming this. The present cross-over study aimed to investigate the short-term effects on appetite and food intake of 48 g of whole-grain wheat (daily for 3 weeks) compared with refined grain (control). A total of fourteen healthy normal-weight adults consumed, within their habitual diets, either two whole-grain bread rolls (providing 48 g of whole grains over two rolls) or two control rolls daily for 3 weeks. Changes in food intake were assessed using 7 d diet diaries. Changes in subjective appetite ratings and food intake were also assessed at postprandial study visits. There were no significant differences between interventions in energy intake (assessed by the 7 d diet diaries and at the ad libitum test meal), subjective appetite ratings or anthropometric measurements. However, there was a significant difference between interventions for systolic blood pressure, which decreased during the whole-grain intervention and increased during the control intervention ( − 2 v. 4 mmHg; P = 0·015). The present study found no effect of whole grains on appetite or food intake in healthy individuals; however, 48 g of whole grain consumed daily for 3 weeks did have a beneficial effect on systolic blood pressure. The findings from the present study therefore do not support epidemiological evidence that whole grains are beneficial in weight regulation, although further investigation in other population groups (such as overweight and obese) would be required.