Greater dietary variety is associated with better biochemical nutritional status in Spanish children: the Four Provinces Study

BACKGROUND AND AIM: Although dietary variety has been associated with a better nutritional profile, its possible role in obesity raises doubts about its overall health benefits. In this study, we examined the association between dietary variety and anthropometric variables, food intake and various food intake biomarkers in Spanish children. METHODS AND RESULTS: This was a cross-sectional study of 1112 children aged 6-7 years from Cadiz, Murcia, Orense and Madrid, who were selected by means of the random cluster-sampling of schools. Information concerning food and nutrient intake was obtained using a food frequency questionnaire, and a dietary variety index (DVI) was calculated on the basis of the number of different foods consumed more than once a month. The anthropometric variables (weight and height), and plasma lipid and vitamin levels were determined using standardised methods. Our results show that the body mass index (BMI) did not vary substantially as a function of DVI: it was 16.9 in the lowest DVI tertile and 17.2 in the highest (p=0.20). Unlike BMI, the DVI positively correlated (p<0.05) with the plasma levels of alpha and beta-carotene, lycopene, retinol, alpha-tocopherol and vitamin E, with energy intake, and with most of the foods, particularly vegetables, fruit and sausages (respective correlation coefficients of 0.43, 0.26 and 0.23). CONCLUSIONS: Dietary variety is associated with a better food and nutritional profile in Spanish children. Nevertheless, the presence of a positive association between the DVI and energy intake, and the consumption of sausages and pre-cooked products calls for the recommendation of a varied diet of healthy foods, such as cereals (especially whole grains), fruits and vegetables

Insulin and HOMA in Spanish prepubertal children: Relationship with lipid profile.

Objective: The effects of insulin or insulin resistance on the lipid profile seem to change with age. The aim of this study was to analyze insulin levels and an insulin resistance index and to investigate the relationship between these and the lipid profile in a population-based sample of Spanish prepubertal children. Methods: 1048 (524 boys and 524 girls) randomly selected prepubertal children were studied. Children were 6 to 8 years old with a mean age of 6.7. Plasma lipid, FFA and insulin levels were measured. The homeostatic model assessment (HOMA) was calculated as an indicator of insulin resistance. Results: When analyzing percentile values of insulin, HOMA and FFA by sex, we observed that girls had significantly higher insulin concentrations than boys (except at the 10th percentile) and significantly higher FFA (except at the 90th percentile) with no significant differences between sexes for HOMA. Multivariate regression analyses showed that insulin was positively associated with glucose, triglycerides and apoB in boys but not in girls, and negatively associated with FFA in both genders. Conclusions: We report here data about the distribution of insulin in the Spanish prepubertal population. The higher levels of insulin in prepubertal girls could indicate that girls start to be more insulin resistant than boys at this age, although other manifestations of insulin resistance are not yet detectable.pre-print211 K

Inhibition of cholesterol biosynthesis by Delta22-unsaturated phytosterols via competitive inhibition of sterol Delta24-reductase in mammalian cells.

Dietary phytosterols are cholesterol-lowering agents that interfere with the intestinal absorption of cholesterol. In the present study, we have studied their effects on cholesterol biosynthesis in human cells, particularly in the sterol-conversion pathway. For this, both Caco-2 (intestinal mucosa) and HL-60 (promyelocytic) human cell lines were incubated with [(14)C]acetate, and the incorporation of radioactivity into sterols was determined using HPLC and radioactivity detection online. Sterols containing a double bond at C-22 in the side chain (stigmasterol, brassicasterol and ergosterol) dramatically inhibited the activity of sterol Delta(24)-reductase, as indicated by the decrease in radioactivity incorporation into cholesterol and the accumulation of its precursors (mainly desmosterol). Phytosterols with the saturated side chain (beta-sitosterol and campesterol) were inactive in this regard. The inhibition of sterol (24)-reductase was confirmed in rat liver microsomes by using (14)C-labelled desmosterol as the substrate. The (22)-unsaturated phytosterols acted as competitive inhibitors of sterol (24)-reductase, with K(i) values (41.1, 42.7 and 36.8 microM for stigmasterol, brassicasterol and ergosterol respectively) similar to the estimated K(m) for desmosterol (26.3 microM). The sterol 5,22-cholestedien-3beta-ol, an unusual desmosterol isomer that lacks the alkyl groups characteristic of phytosterols, acted as a much stronger inhibitor of (24)-reductase (K(i)=3.34 microM). The usually low intracellular concentrations of the physiological substrates of (24)-reductase explains the strong inhibition of cholesterol biosynthesis that these compounds exert in cells. Given that inhibition of sterol (24)-reductase was achieved at physiologically relevant concentrations, it may represent an additional mechanism for the cholesterol-lowering action of phytosterols, and opens up the possibility of using certain (22)-unsaturated sterols as effective hypocholesterolaemic agents

Bioavailability of the antihypertensive peptide LHLPLP: Transepithelial flux of HLPLP

The β-casein peptide f(133-138), with the sequence LHLPLP, was responsible for the angiotensin converting enzyme (ACE)-inhibitory and antihypertensive activity of fermented milk produced with different Enterococcus faecalis strains. The aim of this study was to investigate if the ACE-inhibitory peptide LHLPLP is resistant to brush border peptidases and to examine its mechanism for transepithelial transport using Caco-2 cells. LHLPLP was hydrolysed by cellular peptidases to HLPLP prior to transport across the intestinal epithelium. The effect of some inhibitors on the transport of HLPLP indicated that paracellular passive diffusion is likely the main mechanism of transport across the cell layer. This was confirmed by measuring the flux of the peptide after reversion of the flux from the basolateral to the apical chamber. In vitro incubation HLPLP in human plasma showed that the peptide remained practically intact 1 h after incubation, and degradation to one half was observed at 2 h of incubation.This work has received financial support from Projects AGL2005-03381 and AGL2004-07075-C02-01 (Ministerio de Educación y Ciencia, Spain) and from Projects SAF2005-7308 and CM-S0505-AGR-0153. A.D. is the recipient of a post-doctorate scholarship from the Instituto de Salud Carlos III, Spain

Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport

Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages.This work was supported by the Instituto de Salud Carlos III (grants PI1102077 to D.G.-C. and PI1401648 to F.B.-V.), Ministerio de Economía y Competitividad (grant SAF2015-70747-R to M.A.L.), Plan Nacional de Investigación, Desarrollo e Innovación 2008–2011, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, European Regional Development Fund (ERDF/FEDER), European Cooperation in Science and Technology (COST) action BM0904 and Program ALIBIRD S2013/ABI-2728, Comunidad de Madrid, Spain. CIBEROBN and CIBERDEM are initiatives of the Instituto de Salud Carlos III, Spain.Peer Reviewe