The increasing incidence of the metabolic syndrome (MetS), a combination of risk factors before the onset of CVD and type 2 diabetes, encourages studies on the role of functional food components such as long-chain n-3 PUFA as preventive agents. In the present study, we explore the effect of EPA and DHA supplementation in different proportions on spontaneously hypertensive obese (SHROB) rats, a model for the MetS in a prediabetic state with mild oxidative stress. SHROB rats were randomised into four groups (n 7), each supplemented with EPA/DHA at ratios of 1:1, 2:1 and 1:2, or soyabean oil as the control for 13 weeks. The results showed that in all the proportions tested, EPA/DHA supplementation significantly lowered total and LDL-cholesterol concentrations, compared with those of the control group. EPA/DHA supplementation at the ratios of 1:1 and 2:1 significantly decreased inflammation (C-reactive protein levels) and lowered oxidative stress (decreased excretion of urinary isoprostanes), mainly at the ratio of 1:2. The activity of antioxidant enzymes increased in erythrocytes, abdominal fat and kidneys, with magnitudes depending on the EPA:DHA ratio. PUFA mixtures from fish affected different MetS markers of CVD risk factors in SHROB rats, depending on the ratios of EPA/DHA supplementation. The activation of endogenous defence systems may be related to the reduction of inflammation and oxidative stress.

Various foods are associated with effects against metabolic diseases such as insulin resistance and type 2 diabetes; however, their mechanisms of action are mostly unclear. Fatty acids may contribute by acting as precursors of signalling molecules or by direct activity on receptors. The medium- and long-chain NEFA receptor FFA1 (free fatty acid receptor 1, previously known as GPR40) has been linked to enhancement of glucose-stimulated insulin secretion, whereas FFA4 (free fatty acid receptor 4, previously known as GPR120) has been associated with insulin-sensitising and anti-inflammatory effects, and both receptors are reported to protect pancreatic islets and promote secretion of appetite and glucose-regulating hormones. Hypothesising that FFA1 and FFA4 mediate therapeutic effects of dietary components, we screened a broad selection of NEFA on FFA1 and FFA4 and characterised active compounds in concentration–response curves. Of the screened compounds, pinolenic acid, a constituent of pine nut oil, was identified as a relatively potent and efficacious dual FFA1/FFA4 agonist, and its suitability for further studies was confirmed by additional in vitro characterisation. Pine nut oil and free and esterified pure pinolenic acid were tested in an acute glucose tolerance test in mice. Pine nut oil showed a moderately but significantly improved glucose tolerance compared with maize oil. Pure pinolenic acid or ethyl ester gave robust and highly significant improvements of glucose tolerance. In conclusion, the present results indicate that pinolenic acid is a comparatively potent and efficacious dual FFA1/FFA4 agonist that exerts antidiabetic effects in an acute mouse model. The compound thus deserves attention as a potential active dietary ingredient to prevent or counteract metabolic diseases.

The Mediterranean diet (MD) emerged as a healthy food regimen long before it could be recognised which nutrients or foods were responsible for its observed benefits, and it was only in the middle of the last century that the first scientific approach ‘The Seven Countries Study’ appeared. Epidemiological and anthropological studies of the MD converged, first by investigating at single nutrients or foods, then by adopting the more holistic approach of dietary patterns (DP), and now with a molecular approach. These studies resulted in convincing evidence that a MD decreases the risk of all-cause mortality and cardiovascular mortality and incidence. A risk reduction of developing type 2 diabetes is probable. Evidence is less stringent for other metabolic diseases and all cancers but from possible to probable for some cancer sites. Although DP showed that the MD has to be considered in its totality, olive oil could have a specific role. Lifestyle factors such as physical activity for energy balance, outdoor life for vitamin D synthesis and conviviality are also probably partly responsible for the health benefits. The MD is a lifestyle well suited for coping not only with personal health but also with wider societal concerns in relation to environment, public health and economy.

In the present study, the effects of partial substitution of dietary protein by digestible starch on endogenous glucose production were evaluated in European seabass (Dicentrarchus labrax). The fractional contribution of dietary carbohydrates v. gluconeogenesis to blood glucose appearance and hepatic glycogen synthesis was quantified in two groups of seabass fed with a diet containing 30 % digestible starch (DS) or without a carbohydrate supplement as the control (CTRL). Measurements were performed by transferring the fish to a tank containing water enriched with 5 % 2H2O over the last six feeding days, and quantifying the incorporation of 2H into blood glucose and hepatic glycogen by 2H NMR. For CTRL fish, gluconeogenesis accounted for the majority of circulating glucose while for the DS fish, this contribution was significantly lower (CTRL 85 (sem 4) % v. DS 54 (sem 2) %; P< 0·001). Hepatic glycogen synthesis via gluconeogenesis (indirect pathway) was also significantly reduced in the DS fish, in both relative (CTRL 100 (sem 1) % v. DS 72 (sem 1) %; P< 0·001) and absolute terms (CTRL 28 (sem 1) v. DS 17 (sem 1) μmol/kg per h; P< 0·001). A major fraction of the dietary carbohydrates that contributed to blood glucose appearance (33 (sem 1) % of the total 47 (sem 2) %) had undergone exchange with hepatic glucose 6-phosphate. This indicated the simultaneous activity of hepatic glucokinase and glucose 6-phosphatase. In conclusion, supplementation of digestible starch resulted in a significant reduction of gluconeogenic contributions to systemic glucose appearance and hepatic glycogen synthesis.

In the present study, a linear regression analysis between lysine intake and lysine retention was conducted to investigate the efficiency of lysine utilisation (kLys) at marginal lysine intake of either protein-bound or free lysine sources in juvenile turbot (Psetta maxima). For this purpose, nine isonitrogenous and isoenergetic diets were formulated to contain 2·25–4·12 g lysine/100 g crude protein (CP) to ensure that lysine was the first-limiting amino acid in all diets. The basal diet contained 2·25 g lysine/100 g CP. Graded levels of casein (Cas), fishmeal (FM) and l-lysine HCl (Lys) were added to the experimental diets to achieve stepwise lysine increments. A total of 240 fish (initial weight 50·1 g) were hand-fed all the experimental diets once daily until apparent satiation over a period of 56 d. Feed intake was significantly affected by dietary lysine concentration rather than by dietary lysine source. Specific growth rate increased significantly at higher lysine concentrations (P< 0·001). CP, crude lipid and crude ash contents in the whole body were affected by the dietary treatments. The linear regression slope between lysine retention and lysine intake (kLys) was similar between all the dietary lysine sources. The kLys values for the diets supplemented with Cas, Lys or FM were 0·833, 0·857 and 0·684, respectively. The bioavailability of lysine from the respective lysine sources was determined by a slope-ratio approach. The bioavailability of lysine (relative to the reference lysine source Cas) from FM and Lys was 82·1 and 103 %, respectively. Nutrient requirement for maintenance was in the range of 16·7–23·4 mg/kg0·8 per d, and did not differ between the treatments. There were no significant differences in lysine utilisation efficiency or bioavailability of protein-bound or crystalline lysine from the respective sources observed when lysine was confirmed to be the first-limiting nutrient.

Pathogenic invasion by Escherichia coli and Salmonellae remains a constant threat to the integrity of the intestinal epithelium and can rapidly induce inflammatory responses. At birth, colostrum consumption exerts numerous beneficial effects on the properties of intestinal epithelial cells and protects the gastrointestinal tract of newborns from pathogenic invasion. The present study aimed to investigate the effect of colostrum on the early and late inflammatory responses induced by pathogens. The short-term (2 h) and long-term (24 h) effects of exposure to heat-killed (HK) E. coli and Salmonella enterica Typhimurium on gene expression in the porcine intestinal epithelial cell (IPEC-J2) model were first evaluated by microarray and quantitative PCR analyses. Luciferase assays were performed using a NF-κB-luc reporter construct to investigate the effect of colostrum whey treatment on the activation of NF-κB induced by HK bacteria. Luciferase assays were also performed using NF-κB-luc, IL-8-luc and IL-6-luc reporter constructs in human colon adenocarcinoma Caco-2/15 cells exposed to dose–response stimulations with HK bacteria and colostrum whey. Bovine colostrum whey treatment decreased the expression of early and late inflammatory genes induced by HK bacteria in IPEC-J2, as well as the transcriptional activation of NF-κB-luc induced by HK bacteria. Unlike that with colostrum whey, treatment with other milk fractions failed to decrease the activation of NF-κB-luc induced by HK bacteria. Lastly, the reduction of the HK bacteria-induced activation of NF-κB-luc, IL-8-luc and IL-6-luc by colostrum whey was dose dependent. The results of the present study indicate that bovine colostrum may protect and preserve the integrity of the intestinal mucosal barrier in the host by controlling the expression levels of early and late inflammatory genes following invasion by enteric pathogens.

About 20 % of ruminal microbial N in dairy cows derives from purines and pyrimidines; however, their intermediary metabolism and contribution to the overall N metabolism has sparsely been described. In the present study, the postprandial patterns of net portal-drained viscera (PDV) and hepatic metabolism were assessed to evaluate purine and pyrimidine N in dairy cows. Blood was sampled simultaneously from four veins with eight hourly samples from four multi-catheterised Holstein cows. Quantification of twenty purines and pyrimidines was performed with HPLC–MS/MS, and net fluxes were estimated across the PDV, hepatic tissue and total splanchnic tissue (TSP). Concentration differences between veins of fifteen purine and pyrimidine nucleosides (NS), bases (BS) and degradation products (DP) were different from zero (P≤ 0·05), resulting in the net PDV releases of purine NS (0·33–1·3 mmol/h), purine BS (0·0023–0·018 mmol/h), purine DP (7·0–7·8 mmol/h), pyrimidine NS (0·30–2·8 mmol/h) and pyrimidine DP (0·047–0·77 mmol/h). The hepatic removal of purine and pyrimidine was almost equivalent to the net PDV release, resulting in no net TSP release. One exception was uric acid (7·9 mmol/h) from which a large net TSP release originated from the degradation of purine NS and BS. A small net TSP release of the pyrimidine DP β-alanine and β-aminoisobutyric acid ( − 0·032 to 0·37 mmol/h) demonstrated an outlet of N into the circulating N pool. No effect of time relative to feeding was observed (P>0·05). These data indicate that considerable amounts of N are lost in the dairy cow due to prominent intermediary degradation of purines, but that pyrimidine N is reusable to a larger extent.

Randomised controlled trials (RCT) testing the effects of antioxidant supplements on endothelial function (EF) have reported conflicting results. We aimed to investigate the effects of supplementation with antioxidant vitamins C and E on EF and to explore factors that may provide explanations for the inconsistent results. We searched four databases (MEDLINE, Embase, Cochrane Library and Scopus) from inception until May 2014 for RCT involving adult participants aged ≥ 18 years who were supplemented with vitamins C and E alone or in combination for more than 2 weeks and reporting changes in EF measured using flow mediated dilation or forearm blood flow. Data were pooled as standardised mean difference (SMD) and analysed using a random-effects model. Significant improvements in EF were observed in trials supplementing with vitamin C alone (500–2000 mg/d) (SMD: 0·25, 95 % CI 0·02, 0·49, P= 0·043) and vitamin E alone (300–1800 IU/d; 1 IU vitamin E = 0·67 mg natural vitamin E) (SMD: 0·48, 95 % CI 0·23, 0·72, P= 0·0001), whereas co-administration of both vitamins was ineffective (vitamin C: 500–2000 mg/d; vitamin E: 400–1200 IU/d) (SMD: 0·12, 95 % CI − 0·18, 0·42, P= 0·428). The effect of vitamin C supplementation on EF increased significantly with age (β 0·023, 95 % CI 0·001, 0·05, P= 0·042). There was a significant negative correlation between baseline plasma vitamin E concentration and the effect of vitamin E supplementation on EF (β − 0·03, 95 % CI − 0·06, − 0·001, P= 0·029). Supplementation with either vitamin C or vitamin E alone improves EF. However, subgroup analysis emphasises the importance of careful characterisation and selection of a population group which may benefit from such supplementation.

The main aim of the present study was to investigate the effects of dietary trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) on intestinal microbiota composition and SCFA production. C57BL/6 mice (n 8 per group) were fed a standard diet either supplemented with t10c12-CLA (0·5 %, w/w) (intervention) or with no supplementation (control), daily for 8 weeks. Metabolic markers (serum glucose, leptin, insulin and TAG, and liver TAG) were assessed by ELISA commercial kits, tissue long-chain fatty acids and caecal SCFA by GC, and microbial composition by 16S rRNA pyrosequencing. Dietary t10c12-CLA significantly decreased visceral fat mass (P< 0·001), but did not affect body weight (intervention), when compared with no supplementation (control). Additionally, lipid mass and composition were affected by t10c12-CLA intake. Caecal acetate, propionate and isobutyrate concentrations were higher (P< 0·05) in the t10c12-CLA-supplemented group than in the control group. The analysis of the microbiota composition following 8 weeks of t10c12-CLA supplementation revealed lower proportions of Firmicutes (P= 0·003) and higher proportions of Bacteroidetes (P= 0·027) compared with no supplementation. Furthermore, t10c12-CLA supplementation for 8 weeks significantly altered the gut microbiota composition, harbouring higher proportions of Bacteroidetes, including Porphyromonadaceae bacteria previously linked with negative effects on lipid metabolism and induction of hepatic steatosis. These results indicate that the mechanism of dietary t10c12-CLA on lipid metabolism in mice may be, at least, partially mediated by alterations in gut microbiota composition and functionality.

CVD remains the major cause of death for dialysis patients. Dialysis patients have both traditional and nontraditional risk factors, including the retention of advanced glycation end products (AGE). Tissue AGE can be measured by skin autofluorescence (SAF) and are a reliable measurement of chronic exposure. Dietary intake of AGE may be lower in vegetarian patients than in non-vegetarian patients, so we determined whether vegetarian patients had lower SAF than non-vegetarian patients. We measured SAF in 332 adult haemodialysis patients using a UV technique in a standardised manner. Information about patients' demographic data, laboratory results and current medicinal prescriptions was collected retrospectively from the hospital's computerised database. The mean patient age was 65·2 (sd 15·1) years, 64 % were men, 42 % were diabetic, and 66 % were Caucasian. The mean SAF was 3·26 (sd 0·95) arbitrary units (AU), and SAF was lower in vegetarians as compared to non-vegetarians (2·71 (sd 0·6) v. 3·31 (sd 0·97) AU, P= 0·002). SAF was negatively correlated on both univariate (r − 0·17, P= 0·002) and multiple linear regression (β coefficient − 0·39, 95 % CI − 0·7, − 0·07, P= 0·019). SAF, a marker of tissue AGE deposition, was reduced in vegetarian haemodialysis patients after correction for known confounders, which suggests that a vegetarian diet may reduce exposure to preformed dietary AGE. Dietary manipulation could potentially reduce tissue AGE and SAF as well as CVD risk, but further prospective studies are warranted to confirm the present findings.

Human life expectancy has been increasing steadily for almost two centuries and is now approximately double what it was at the beginning of the Victorian era. This remarkable demographic change has been accompanied by a shift in disease prevalence so that age is now the major determinant of most common diseases. The challenge is to enhance healthy ageing and to reduce the financial and social burdens associated with chronic ill health in later life. Studies in model organisms have demonstrated that the ageing phenotype arises because of the accumulation of macromolecular damage within the cell and that the ageing process is plastic. Nutritional interventions that reduce such damage, or which enhance the organism's capacity to repair damage, lead to greater longevity and to reduced risk of age-related diseases. Dietary (energy) restriction increases lifespan in several model organisms, but it is uncertain whether it is effective in primates, including humans. However, excess energy storage leading to increased adiposity is a risk factor for premature mortality and for age-related diseases so that obesity prevention is likely to be a major public health route to healthy ageing. In addition, adherence to healthy eating patterns, such as the Mediterranean dietary pattern, is associated with longevity and reduced risk of age-related diseases.

Body fat distribution, especially visceral fat accumulation, may contribute more than total fat mass per se to the development of metabolic and cardiovascular disorders. Early prevention highly improves health outcomes later in life, especially when considering such cumulative conditions as atherosclerosis. However, as these processes emerge to be partly reversible, dietary and lifestyle interventions at any age and health condition are greatly beneficial. Given the worldwide abundance of metabolic and cardiovascular disorders, the identification and implementation of strategies for preventing or reducing the accumulation of morbid fat tissues is of great importance for preventing and regressing atherosclerosis. This review focuses on dietary strategies and specific food components that were demonstrated to alter body fat distribution and regression of atherosclerosis. Different properties of various adipose depots (superficial subcutaneous, deep subcutaneous and visceral fat depots) and their contribution to metabolic and cardiovascular disorders are briefly discussed. Visceral obesity and atherosclerosis should be approached as modifiable rather than ineluctable conditions.

Both Fe deficiency and poor n-3 fatty acid status have been associated with behavioural changes in children. In the present study, we investigated the effects of Fe and DHA+EPA supplementation, alone or in combination, on physical activity during school days and on teacher-rated behaviour in healthy Fe-deficient school children. In a 2 × 2 factorial design, children (n 98, 6–11 years) were randomly assigned to receive (1) Fe (50 mg) plus DHA (420 mg)+EPA (80 mg), (2) Fe plus placebo, (3) placebo plus DHA+EPA or (4) placebo plus placebo as oral supplements (4 d/week) for 8·5 months. Physical activity was measured during four school days at baseline and endpoint using accelerometers, and data were stratified into morning class time (08.00–10.29 hours), break time (10.30–11.00 hours) and after-break class time (11.01–12.00 hours) for analysis. Classroom behaviour was assessed at endpoint using Conners’ Teacher Rating Scales. DHA+EPA supplementation decreased physical activity counts during morning class time, increased sedentary physical activity, and decreased light- and moderate-intensity physical activities. Consistently, DHA+EPA supplementation increased sedentary physical activity and decreased light-intensity physical activity during after-break class time. Even though there were no treatment effects found on teacher-rated behaviour, lower physical activity during morning class time was associated with lower levels of teacher-rated hyperactivity and oppositional behaviour at endpoint. Despite a positive association between Fe status and physical activity during break time at baseline, Fe supplementation did not affect physical activity during break time and class time. Our findings suggest that DHA+EPA supplementation may decrease physical activity levels during class time, and further indicate that accelerometry might be a useful tool to assess classroom behaviour in healthy children.

The aim of the present study was to describe age-related changes in anatomic, functional and microbial variables during the rumen development process, as affected by the feeding system (supplemental feeding v. grazing), in goats. Goats were slaughtered at seven time points that were selected to reflect the non-rumination (0, 7 and 14 d), transition (28 and 42 d) and rumination (56 and 70 d) phases of rumen development. Total volatile fatty acid (TVFA) concentration (P= 0·002), liquid-associated bacterial and archaeal copy numbers (P< 0·01) were greater for supplemental feeding v. grazing, while rumen pH (P< 0·001), acetate molar proportion (P= 0·003) and solid-associated microbial copy numbers (P< 0·05) were less. Rumen papillae length (P= 0·097) and extracellular (P= 0·093) and total (P= 0·073) protease activity potentials in supplemented goats tended to be greater than those in grazing goats. Furthermore, from 0 to 70 d, irrespective of the feeding system, rumen weight, rumen wall thickness, rumen papillae length and area, TVFA concentration, xylanase, carboxymethylcellulase activity potentials, and microbial copy numbers increased (P< 0·01) with age, while the greatest amylase and protease activity potentials occurred at 28 d. Most anatomic and functional variables evolved progressively from 14 to 42 d, while microbial colonisation was fastest from birth to 28 d. These outcomes suggest that the supplemental feeding system is more effective in promoting rumen development than the grazing system; in addition, for both the feeding systems, microbial colonisation in the rumen is achieved at 1 month, functional achievement at 2 months, and anatomic development after 2 months.

Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

It is hypothesised that during immune system activation, there is a competition for amino acids (AA) between body protein deposition and immune system functioning. The aim of the present study was to quantify the effect of immune system activation on N retention and AA metabolism in growing pigs, depending on dietary protein supply. A total of sixteen barrows received an adequate (Ad) or restricted (Res) amount of dietary protein, and were challenged at day 0 with intravenous complete Freund's adjuvant (CFA). At days − 5, 3 and 8, an irreversible loss rate (ILR) of eight AA was determined. CFA successfully activated the immune system, as indicated by a 2- to 4-fold increase in serum concentrations of acute-phase proteins (APP). Pre-challenge C-reactive protein concentrations were lower (P< 0·05) and pre- and post-challenge albumin tended to be lower in Res-pigs. These findings indicate that a restricted protein supply can limit the acute-phase response. CFA increased urinary N losses (P= 0·04) and tended to reduce N retention in Ad-pigs, but not in Res-pigs (P= 0·07). The ILR for Val was lower (P= 0·05) at day 8 than at day 3 in the post-challenge period. The ILR of most AA, except for Trp, were strongly affected by dietary protein supply and positively correlated with N retention. The correlations between the ILR and APP indices were absent or negative, indicating that changes in AA utilisation for APP synthesis were either not substantial or more likely outweighed by a decrease in muscle protein synthesis during immune system activation in growing pigs.

Chronic ingestion of apple pectin has been shown to increase the absorption of quercetin in rats. The present study was designed to elucidate whether the simultaneous ingestion of quercetin with apple pectin could enhance the absorption of quercetin in humans, and the effects of dose dependency and degree of pectin methylation on quercetin absorption were also investigated. Healthy volunteers (n 19) received 200 ml of 0·5 mg/ml of quercetin drinks with or without 10 mg/ml of pectin each in a randomised cross-over design study with over 1-week intervals; urine samples from all the subjects were collected within 24 h after ingestion of the test drinks, and urinary deconjugated quercetin and its metabolites were determined using HPLC. The sum of urinary quercetin and its metabolites excreted was increased by 2·5-fold by the simultaneous ingestion of pectin. The metabolism of methylated quercetin (isorhamnetin and tamarixetin) was not affected by pectin ingestion. In six volunteers, who received quercetin drinks containing 0, 3 and 10 mg/ml of pectin, the sum of urinary quercetin and its metabolites excreted also increased in a pectin dose-dependent manner. Furthermore, the simultaneous ingestion of quercetin with low-methoxy and high-methoxy pectin, respectively, increased the sum of urinary excretion of quercetin and its metabolites by 1·69-fold and significantly by 2·13-fold compared with the ingestion of quercetin without pectin. These results elucidated that apple pectin immediately enhanced quercetin absorption in human subjects, and that its enhancing effect was dependent on the dose and degree of pectin methylation. The results also suggested that the viscosity of pectin may play a role in the enhancement of quercetin absorption.

Lactobacillus rhamnosus GG, Lactobacillusparacasei TMC0409, Streptococcus thermophilus TMC1543 and whey proteins were used to prepare fermented milk. For the experiment aP2–agouti transgenic mice were pre-treated with a high-sucrose/high-fat diet for 6 weeks to induce obesity. The obese mice were fed a diet containing 1·2 % Ca and either non-fat dried milk (NFDM) or probiotic-fermented milk (PFM) with nutritional energy restriction for 6 weeks. The animals were examined after the treatment for changes in body weight, fat pad weight, fatty acid synthase (FAS) activity, lypolysis, the expression levels of genes related to lipid metabolism, insulin sensitivity in adipocytes and skeletal muscle and the presence of biomarkers for oxidative and inflammatory stress in plasma. It was found that the PFM diet significantly reduced body weight, fat accumulation, and adipocyte FAS activity, and increased adipocyte lipolysis as compared with the effects of the NFDM diet (P< 0·05). The adipose tissue gene expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) was significantly suppressed in mice that were fed PFM as compared with those that were fed NFDM (P< 0·05). PFM caused a greater up-regulation of skeletal muscle PPARα, PPARδ, uncoupling protein 3 (UCP3) and GLUT4 expression and a significant decrease in the plasma concentration of insulin, malondialdehyde, TNF-α, monocyte chemotactic protein-1 and C-reactive protein as compared with the effects of NFDM (P< 0·05). Fermentation of milk with selected probiotics and supplementation of milk with whey proteins may thus enhance anti-obesity effects of Ca and dairy products by the suppression of adipose tissue lipogenesis, activation of fat oxidation in skeletal muscle and reduction of oxidative and inflammatory stress.

The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.

There is evidence for health benefits from ‘Palaeolithic’ diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.