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David Southgate will always be known for his work on the composition of foods and the compilation of food tables, and for his innovation in the field of dietary carbohydrate analysis, especially dietary fibre, in which he was the natural heir to McCance and Widdowson, with whom he worked in his early years.

In this issue of the British Journal of Nutrition, Mursu et al.(1) have reported the association between flavonoid intake, cardiovascular mortality and ischaemic stroke among a group of participants in the Kuopio Ischaemic Heart Disease Risk Factor Study.

We have previously reported that dietary fructose rapidly induces jejunal sucrase–isomaltase (SI) gene expression in rats. In this study, we confirmed in mice that SI mRNA was induced 6 h after force-feeding fructose, but not glucose. Using the chromatin immunoprecipitation assay, we revealed that histones H3 and H4 on the promoter/enhancer regions of the SI gene in mice given fructose were highly acetylated, compared with those given glucose or water. These results suggest that acute induction of SI gene expression by dietary fructose is associated with acetylation of histones H3 and H4 on the SI gene.

As part of the rapid socio-cultural transition observed in Arctic populations, the Inuit diet is changing. We present original data derived from the baseline Inuit Health in Transition cohort study regarding biological levels of n-3 fatty acids and trans-fatty acids (TFA), lipids with opposite health effects found respectively in traditional marine diets and recently introduced low-quality imported foods. A total of 524 Inuit from the Disko Bay area (Greenland) and 888 Inuit from the fourteen communities of Northern Québec (Nunavik) participated in the study. We measured the fatty acid profile of erythrocyte (RBC) membrane phospholipids (PL) as a surrogate for individual intakes. Moreover, the contribution of store-bought foods to energy intakes was assessed through dietary questionnaires. Our results show that while n-3 fatty acid levels were slightly lower in Nunavik (9·4 % of RBC membrane PL) than in Greenland (12·1 %), TFA levels were on average nearly thrice as high in Nunavik Inuit (1·20 %) as they were in Greenlanders (0·43 %). Moreover, younger Nunavik Inuit accumulated higher intakes of TFA and lower intakes of n-3 fatty acids. Finally, the average proportion of energy derived from store-bought foods was high in both groups (77·5 % and 83·5 %), especially in youth. Our results call for action to rehabilitate and recover access to country foods and point to the importance for Nunavik and the entire circumpolar world to follow the example of Denmark and Greenland, which imposed a maximum content of 2 g/100 g fat on industrially produced trans-fats in 2003.

The biological activities of a protein isolate from lupin (Lupinus albus) were studied in a rabbit model of atherosclerosis. Focal plaque development was induced at both common carotid arteries by perivascular injury. After surgery, animals were fed three different diets for 90 d, all with 1 % cholesterol, 15 % SFA and 20 % protein; the protein source was casein (CAS), lupin proteins (LUP) or 50 % CAS+50 % LUP (CAS+LUP). Lower cholesterolaemia was detected in the LUP v. the CAS group at 60 and 90 d of treatment ( − 40·3 and − 33·5 %, respectively; P < 0·05). Cryosection analyses of the carotids indicated a significant reduction in focal lesion progression in the LUP v. the CAS group ( − 37·4 %; P < 0·05). In summary, in a rabbit model of atherosclerosis, a protein isolate from L. albus reduced cholesterolaemia and exerted a remarkable protective activity against atherosclerosis progression.

Fermentation of carbohydrates in the colon can stimulate cell proliferation and could thus be a cancer risk. The effects of resistant carbohydrates, i.e. those not digested and absorbed in the small intestine, on cell proliferation, crypt fission and polyp development were investigated in wild-type and adenomatous polyposis coli multiple intestinal neoplasia (ApcMin/+) mice. Fifteen 4-week-old female wild-type and fifteen ApcMin/+ mice were used for each group and fed a chow diet, a semi-synthetic diet or the semi-synthetic supplemented with wheat bran or an apple pomace preparation, both high in resistant carbohydrates, for 8 weeks. Tissue from all mice was used to measure cell proliferation and crypt fission and tissue from the ApcMin/+ mice was scored for polyp number and tumour burden. There were slight reductions in intestinal mass in the mice fed the semi-synthetic diets and this was increased by the inclusion of resistant carbohydrates. The ApcMin/+ mice had elevated cell proliferation and crypt fission in the distal small intestine and colon and these were increased by the resistant carbohydrates. Bran or apple pomace significantly increased polyp number in the proximal third of the small intestine. Apple pulp more than doubled polyp number throughout the small bowel (99·2 (sem 11·1) v. 40·0 (sem 8·2), P < 0·004). Bran and apple pomace increased polyp diameter and hence burden in the colon by 243 and 150 %, respectively (P < 0·05). In conclusion, both types of resistant carbohydrates increased polyp number and tumour burden and this was associated with elevated epithelial cell proliferation and crypt fission.

In order to study the effects of dietary lipids and vitamin A on the development of adipose tissues, young rats were submitted for 8 d to a control or to two cafeteria diets with normal (Caf) or higher (Caf+) vitamin A levels. Retinoid (retinoic acid receptor (RAR) α, RARγ, retinoid X receptor (RXR) α) and fatty acid (PPARγ) receptor mRNA was measured in the subcutaneous white adipose tissue (Swat) and in isolated mature adipocytes by RT-PCR. The stroma vascular fraction was cultured in vitro to test the capacities of the adipocyte precursors to proliferate and differentiate. The Caf diet enriched in vitamin A resulted in an increased adiposity, due to increased adipocyte hypertrophy. This was concomitant with a lower expression of RARα and RARγ mRNA ( − 34·6 and − 38·6 %) and a higher expression of PPARγ (+59 %) in the Swat and, to a less extent, in isolated adipocytes. Positive correlations were obtained between PPARγ mRNA and Swat weights and between PPARγ and RXRα mRNA. By contrast, RARγ mRNA and Swat masses were negatively correlated. The adipocyte precursors from Caf+ Swat proliferated more, in vitro, at the beginning of the culture. This difference progressively disappeared and was totally absent after 8 d of culture, but with a higher percentage of differentiated preadipocytes (+80·3 %) in the Caf+ group. In conclusion, lipids and vitamin A act synergistically on the normal growth of the adipose tissue in young rats, concomitant with an imbalance in the pattern of the nuclear receptors. These changes influence the early normal development of the endogenous adipocyte precursors.

The migration and matrix metalloproteinase (MMP) activation of vascular smooth muscle cells may play key roles in the development of atherosclerosis. Carnosic acid (CA) is a phenolic compound found in herbs, including rosemary and sage. Previous studies indicated that CA possesses antioxidant activity in vitro. In this study, we investigated the effects of CA on TNF-α-induced cell migration, the formation of intracellular reactive oxygen species, the translocation of NF-κB and the activation and expression of MMP-9 in human aortic smooth muscle cells (HASMC). The Matrigel migration assay showed that CA (10 and 20 μmol/l) effectively inhibited TNF-α-induced migration of HASMC as compared with the control group. To explain this inhibitory effect, MMP-9 was assayed by gelatin zymography and Western blot. The results indicated that CA inhibited MMP-9 activity and expression. Furthermore, the production of reactive oxygen species and the nuclear translocation of NF-κB p50 and p65 induced by TNF-α were dose-dependently suppressed by CA pretreament. These results indicate that CA has anti-inflammatory properties and may prevent the migration of HASMC by suppressing MMP-9 expression through down-regulation of NF-κB.

Epidemiological studies suggest that dietary PUFA may influence breast cancer progression. n-3 PUFA are generally known to exert antitumour effects, whereas reports relative to n-6 PUFA anti-carcinogen effects are controversial. Arachidonic acid (AA; 20 : 4n − 6) and its metabolites have been shown to inhibit the growth of human breast cancer cell lines, even if the downstream mechanisms by which AA may influence carcinogenesis remain unresolved. We explored the molecular basis for AA influence on proliferation, signal transduction and apoptosis in two human breast cancer cell lines, MCF-7 and MDA-MB-231. In both cell lines AA inhibited cell growth in a dose-dependent manner, even if MDA-MB-231 was somewhat more growth-inhibited than MCF-7. AA decreased extracellular signal-regulated protein kinase 1/2 phosphorylation level, and positively modulated PPARγ and PPARα expression, with only a slight effect against PPARβ/δ. In addition, AA increased Bak (an apoptosis-regulating protein) expression and reduced procaspase-3 and -9 levels only in MDA-MB-231 cells, thus indicating that the growth inhibitory effect can be correlated with apoptosis induction. In both cell lines the use of a specific antagonist made it possible to establish a relationship between AA growth inhibitory effect and PPARα involvement. AA decreases cell proliferation most likely by inducing apoptosis in MDA-MB-231 cells, while in the MCF-7 cell line the growth inhibitory activity can be attributed to the inhibition of the signal transduction pathway involved in cell proliferation. In both cases, the results here presented suggest PPARα as a possible contributor to the growth inhibitory effect of AA.

Aqueous extracts or juice from unripened fruit of Momordica charantia (bitter melon) has traditionally been used in the treatment of diabetes and its complications. Insulin resistance is characterized by significant down-regulation of hepatic insulin signalling as documented by attenuated phosphorylation of insulin receptor (IR), IR substrates 1 and 2, phosphoinositide-3 kinase, protein kinase B, and over-expression of phosphotyrosine phosphatase 1B. We recently demonstrated that bitter melon juice (BMJ) is a potent inhibitor of apoB secretion and TAG synthesis and secretion in human hepatoma cells, HepG2, that may be involved in plasma lipid- and VLDL-lowering effects observed in animal studies. The aim of this study was to evaluate the effects of BMJ on plasma apoB levels and hepatic insulin signalling cascade in mice fed high-fat diet (HFD). Female C57BL/6 mice (4–6 weeks old) were randomized into three groups receiving regular rodent chow, HFD and HFD+BMJ. The data indicate that BMJ not only improves glucose and insulin tolerance but also lowers plasma apoB-100 and apoB-48 in HFD-fed mice as well as modulates the phosphorylation status of IR and its downstream signalling molecules. Investigating the biochemical and molecular mechanisms involved in amelioration of diabetic dyslipidaemia by BMJ may lead to identification of new molecular targets for dietary/alternative therapies.

We have previously demonstrated that maternal protein restriction during pregnancy leads to raised blood pressure and endothelial dysfunction in the offspring (F1). Here we show that these characteristics are transmitted to the F2 offspring through the maternal line, in the absence of any additional challenges to the F1. Female Wistar rats were fed either a control (18 % casein) or protein-restricted diet (PR; 9 % casein) throughout pregnancy. Female F1 offspring, maintained on standard chow postpartum, were mated with breeding males to produce F2 progeny. Systolic blood pressure (SBP) in male F2 offspring was assessed by tail-cuff plethysmography at age 100 d and vascular function of small mesenteric arteries by wire myography at age 80 and 200 d. SBP was raised in PR F2 offspring compared with controls (control 122·1 (sem 2·3) mmHg, n 7; PR 134·7 (sem 3·2) mmHg, n 6; P < 0·01) and endothelial function, assessed by vasodilatation to acetylcholine, was impaired at both age 80 d (% maximal response: control 89·7 (sem 2·6), n 14; PR 72·7 (sem 4·4), n 15; P < 0·01) and 200 d (effective concentration equal to 50 % of maximum (pEC50): control 7·67 (sem 0·10), n 10; PR 7·33 (sem 0·07), n 8; P < 0·05). The present study demonstrates that both raised blood pressure and endothelial dysfunction are passed via the maternal line to grand-offspring in the absence of any additional dietary challenges to their F1 mothers. Risk factors for chronic disease may therefore be heritable by non-genomic processes.

In spite of their high oxidisability, long-chain n-3 PUFA protect against CVD. Dietary fatty acids modulate the fatty acid composition of lipoproteins involved in atherosclerosis. We thought that if long-chain n-3 PUFA were able to increase NO production by the aorta, then by its antioxidant activity the NO will prevent lipid peroxidation. However, the beneficial effect of NO in vivo on VLDL+LDL oxidation would only be possible if NO could diffuse to their lipidic core. Rats were fed maize oil- or fish oil as menhaden oil- (MO) rich diets for 8 weeks, to study the effects of MO on aortic NO production, NO diffusion into VLDL+LDL, the extent of oxidation in native VLDL+LDL and their oxidisability ex vivo. Aortic NO production and its α-tocopherol content were increased and n-3 PUFA were incorporated into the VLDL+LDL. In spite of the higher peroxidisability and the low α-tocopherol in native VLDL+LDL from rats fed MO, native VLDL+LDL from the two groups shared similar electrophoretic patterns, conjugated dienes, thiobarbituric acid-reactive substances, total antioxidant capacity, and NO diffusibility on VLDL+LDL, indicative of an in vivo protection against oxidation. However, these results do not correlate with the ex vivo oxidisability of VLDL+LDL, as NO is lacking. Thus, the in vivo beneficial effects can be explained by increased α-tocopherol in aorta and by a compensatory effect of NO on VLDL+LDL against the low α-tocopherol levels, which may contribute to the anti-atherogenic properties of fish oil.

There is growing evidence that dietary proteins may interfere with lipid metabolism. We therefore examined the effects of feeding obese Zucker rats a single cell protein (SCP) with low ratios of methionine:glycine and lysine:arginine for 6 weeks. SCP feeding reduced the hepatic steatosis and lowered the plasma transaminase levels when compared with casein-fed rats (controls). The fatty acid oxidation was increased in liver mitochondria and peroxisomes, whereas the activities of enzymes involved in lipogenesis and TAG biosynthesis were unaffected. SCP feeding affected the fatty acid composition of liver lipids and plasma, and reduced the mRNA levels of the fatty acid desaturases. The decreased gene expression of stearoyl-CoA desaturase suggested that the fatty acids were directed towards oxidation rather than esterification as TAG. The decreased mRNA levels of VLDL-receptor and lipoprotein lipase in the liver after SCP feeding suggested that the uptake of TAG-rich lipoprotein to the liver was decreased. To conclude, the reduced fatty liver by SCP feeding may be caused by the increased capacity for fatty acid β-oxidation in the liver, combined with changed fatty acid composition and possibly a reduced hepatic clearance of circulating VLDL. An increased awareness of the effect of dietary proteins on lipid metabolism could be of relevance in future dietary treatment of non-alcoholic fatty liver disease.

Maize with enhanced provitamin A carotenoids (biofortified), accomplished through conventional plant breeding, maintains vitamin A (VA) status in Mongolian gerbils (Meriones unguiculatus). Two studies in gerbils compared the VA value of β-cryptoxanthin with β-carotene. Study 1 (n 47) examined oil supplements and study 2 (n 46) used maize with enhanced β-cryptoxanthin and β-carotene. After 4 weeks' depletion, seven or six gerbils were killed; remaining gerbils were placed into weight-matched groups of 10. In study 1, daily supplements were cottonseed oil, and 35, 35 or 17·5 nmol VA (retinyl acetate), β-cryptoxanthin or β-carotene, respectively, for 3 weeks. In study 2, one group of gerbils was fed a 50 % biofortified maize diet which contained 2·9 nmol β-cryptoxanthin and 3·2 nmol β-carotene/g feed. Other groups were given equivalent β-carotene or VA supplements based on prior-day intake from the biofortified maize or oil only for 4 weeks. In study 1, liver retinol was higher in the VA (0·74 (sd 0·11) μmol) and β-cryptoxanthin (0·65 (sd 0·10) μmol) groups than in the β-carotene (0·49 (sd 0·13) μmol) and control (0·41 (sd 0·16) μmol) groups (P < 0·05). In study 2, the VA (1·17 (sd 0·19) μmol) and maize (0·71 (sd 0·18) μmol) groups had higher liver retinol than the control (0·42 (sd 0·16) μmol) group (P < 0·05), whereas the β-carotene (0·57 (sd 0·21) μmol) group did not. Bioconversion factors (i.e. 2·74 μg β-cryptoxanthin and 2·4 μg β-carotene equivalents in maize to 1 μg retinol) were lower than the Institute of Medicine values.

Very long-chain n-3 PUFA from fish are suggested to play a role in the development of the brain. Fish oil feeding results in higher proportions of n-3 PUFA in the brains of newborn piglets. However, the effect of fish oil on the fatty acid composition of specific cerebral brain lobes in juvenile pigs is largely uninvestigated. This study examined the effect of a fish oil diet on the fatty acid composition of the frontal, parietal, temporal and occipital brain lobes in juvenile pigs (7 weeks old). Pigs were randomly allocated to a semipurified pig diet containing either 4 % (w/w) fish oil (n 19) or 4 % (w/w) high-oleic acid sunflower oil (HOSF diet, n 18) for a period of 8 weeks. The fish oil diet resulted in significantly higher proportions (%) of DHA in the frontal (10·6 (sd1·2)), parietal (10·2 (sd1·5)) and occipital brain lobes (9·9 (sd 1·3)), but not in the temporal lobe (7·7 (sd1·6)), compared with pigs fed the HOSF diet (frontal lobe, 7·5 (sd1·0); parietal lobe, 8·1 (sd 1·3); occipital lobe, 7·3 (sd1·2), temporal lobe, 6·6 (sd1·2). Moreover, the proportion of DHA was significantly lower in the temporal lobe compared with the frontal, parietal and occipital brain lobes in pigs fed a fish oil diet. In conclusion, the brains of juvenile pigs appear to be responsive to dietary fish oil, although the temporal brain lobe is less responsive compared with the other three brain lobes. The functional consequences of these differences are a challenging focus for future investigation.

Felinine is a branched-chain sulfur amino acid present in the urine of certain Felidae, including domestic cats. The objective of the present study was to determine if additional cystine and/or dietary N would increase felinine and N-acetylfelinine excretion by intact male cats fed a low-protein (LP) diet. Feeding five adult intact male cats an LP diet (18·8 % of metabolisable energy (ME) as protein) v. a high-protein diet (38·6 % of ME as protein) resulted in a trend (P = 0·08) for decreased urinary felinine and no change in N-acetylfelinine excretion. In a 23 d study, when the LP diet was supplemented with l-cystine at 9·3 g/kg DM, urinary felinine:creatinine ratio showed a linear two-fold (121 %) increase (P < 0·01) from 0·24 (sem 0·05) to 0·53 (sem 0·13) after 10 d. Subsequent feeding of the LP diet resulted in a decrease in felinine excretion to base levels. Plasma γ-glutamylfelinylglycine concentrations were consistent with the excretion of felinine. Supplementation of the LP diet with l-cystine (9·3 g/kg DM), dispensable amino acids and arginine to a second group (n 5) also resulted in a significant (P < 0·01) but smaller (+72 %) increase in the daily felinine:creatinine ratio (0·25 (sem 0·04) to 0·43 (sem 0·05)). The degree of felinine N-acetylation within groups was unaffected by dietary addition and withdrawal of amino acids. The results indicate that felinine synthesis is regulated by cystine availability, and that arginine may be physiologically important in decreasing felinine biosynthesis in intact male cats.

Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (sem 2) years, body mass 75·7 (sem 3·2) kg and BMI 23·8 (sem 0·8) kg/m2. Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency (two) meal ingestion (LOFREQMEAL); high-frequency (twelve) meal ingestion (HIFREQMEAL). Meals were equi-energetic within trials, consisting of 64 % carbohydrate, 23 % fat and 13 % protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between trials (P>0·05), although the hormonal response patterns to the two meal feeding regimens were different. An inverse relationship was found between serum insulin and plasma ghrelin during the FAST and LOFREQMEAL trials (P < 0·05); and, in the postprandial period, there was a time delay between insulin responses and successive ghrelin responses. This relationship was not observed during the HIFREQMEAL trial (P>0·05). This study provides further evidence that the postprandial fall in ghrelin might be due, at least partially, to the rise in insulin and that high-frequency feeding may disrupt this relationship.

The objective of the present study was to examine the effects of dietary Zn deficiency on the ex vivo cytokine production (IL-2, interferon-γ (IFN-γ), IL-6 and IL-10) of isolated thymocytes and splenocytes after mitogenic stimulation with concavalin A and to explore the role of corticosterone in this regulation. Weanling rats were assigned to one of four dietary treatments for 3 weeks: Zn-deficient ( < 1 mg Zn/kg diet, ad libitum), pair-fed (30 mg Zn/kg diet, limited to amount of feed as consumed by the Zn-deficient group), marginally Zn-deficient (10 mg Zn/kg diet, ad libitum) and control (30 mg Zn/kg diet, ad libitum). Thymocytes and splenocytes were isolated for cytokine stimulation and determination of T-cell phenotypes. Serum corticosterone concentrations were determined by ELISA. The Zn-deficient and pair-fed groups had 14-fold higher serum corticosterone concentrations compared with the marginally Zn-deficient and control groups (P < 0·0001). The proportions of thymocyte subsets were not altered in the Zn-deficient, pair-fed or marginally Zn-deficient groups; however, thymocyte IL-2 and IL-6 production in these groups was 33–54 % lower compared with the control group (P < 0·05). The Zn-deficient group had an 18–28 % lower proportion of new T-cells (TCRαβ+CD90+), but no difference in the proportion of new T-cells that were cytotoxic or helper. The Zn-deficient group had a 49–62 % lower production of Th1 cytokines (IL-2), but no difference in the production of Th2 cytokines (IL-6, IL-10) by stimulated splenocytes compared with the pair-fed, marginally Zn-deficient and control groups (P < 0·01). These results indicate that Zn status is associated with altered cytokine production, while in vivo corticosterone concentrations are not associated with ex vivo cytokine production.