Restoration of adipose function in obese, glucose-tolerant men following pioglitazone treatment is associated with CCAAT enhancer-binding protein β upregulation

Obese AT (adipose tissue) exhibits increased macrophage number. Pro-inflammatory CD16+ peripheral monocyte numbers are also reported to increase with obesity. The present study was undertaken to simultaneously investigate obesity-associated changes in CD16+ monocytes and ATMs (AT macrophages). In addition, a pilot randomized placebo controlled trial using the PPAR (peroxisome-proliferator-activated receptor) agonists, pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16+ monocytes, ATM and cardiometabolic and adipose dysfunction indices. Obese glucose-tolerant men (n=28) were randomized to placebo, pioglitazone (30 mg/day) and fenofibrate (160 mg/day) for 12 weeks. A blood sample was taken to assess levels of serum inflammatory markers and circulating CD14+/CD16+ monocyte levels via flow cytometry. A subcutaneous AT biopsy was performed to determine adipocyte cell surface and ATM number, the latter was determined via assessment of CD68 expression by IHC (immunohistochemistry) and real-time PCR. Subcutaneous AT mRNA expression of CEBPß (CCAAT enhancer-binding protein ß), SREBP1c (sterol-regulatory-element-binding protein 1c), PPAR?2, IRS-1 (insulin receptor substrate-1), GLUT4 (glucose transporter type 4) and TNFa (tumour necrosis factor a) were also assessed. Comparisons were made between obese and lean controls (n=16) at baseline, and pre- and post-PPAR agonist treatment. Obese individuals had significantly increased adipocyte cell surface, percentage CD14+/CD16+ monocyte numbers and ATM number (all P=0.0001). Additionally, serum TNF-a levels were significantly elevated (P=0.017) and adiponectin levels reduced (total: P=0.0001; high: P=0.022) with obesity. ATM number and percentage of CD14+/CD16+ monocytes correlated significantly (P=0.05). Pioglitazone improved adiponectin levels significantly (P=0.0001), and resulted in the further significant enlargement of adipocytes (P=0.05), without effect on the percentage CD14+/CD16+ or ATM number. Pioglitazone treatment also significantly increased subcutaneous AT expression of CEBPß mRNA. The finding that improvements in obesity-associated insulin resistance following pioglitazone were associated with increased adipocyte cell surface and systemic adiponectin levels, supports the centrality of AT to the cardiometabolic derangement underlying the development of T2D (Type 2 diabetes) and CVD (cardiovascular disease).

The effect of lutein- and zeaxanthin-rich foods v. supplements on macular pigment level and serological markers of endothelial activation inflammation and oxidation pilot studies in healthy volunteers:pilot studies in healthy volunteers

The aim of the present study was to compare the effect of lutein- and zeaxanthin-rich foods and supplements on macular pigment level (MPL) and serological markers of endothelial activation, inflammation and oxidation in healthy volunteers. We conducted two 8-week intervention studies. Study 1 (n 52) subjects were randomised to receive either carrot juice (a carotene-rich food) or spinach powder (a lutein- and zeaxanthin-rich food) for 8 weeks. Study 2 subjects (n 75) received supplements containing lutein and zeaxanthin, ß-carotene, or placebo for 8 weeks in a randomised, double-blind, placebo-controlled trial. MPL, serum concentrations of lipid-soluble antioxidants, inter-cellular adhesion molecule 1, vascular cell adhesion molecule 1, C-reactive protein and F2-isoprostane levels were assessed at baseline and post-intervention in both studies. In these intervention studies, no effects on MPL or markers of endothelial activation, inflammation or oxidation were observed. However, the change in serum lutein and zeaxanthin was associated or tended to be associated with the change in MPL in those receiving lutein- and zeaxanthin-rich foods (lutein r 0.40, P = 0.05; zeaxanthin r 0.30, P = 0.14) or the lutein and zeaxanthin supplement (lutein r 0.43, P = 0.03; zeaxanthin r 0.22, P = 0.28). In both studies, the change in MPL was associated with baseline MPL (food study r - 0.54, P <0.001; supplement study r - 0.40, P <0.001). We conclude that this 8-week supplementation with lutein and zeaxanthin, whether as foods or as supplements, had no significant effect on MPL or serological markers of endothelial activation, inflammation and oxidation in healthy volunteers, but may improve MPL in the highest serum responders and in those with initially low MPL.

Adiponectin multimers, body weight and markers of cardiovascular risk in adolescence: Northern Ireland Young Hearts Project:Northern Ireland Young Hearts Project

Background:Research examining the relationship between adiponectin (AN) isoforms, body weight and cardiovascular (CV) risk factors is limited, particularly in younger populations. Objectives:To investigate the inter-relationships between AN isoforms and CV risk factors, and their dependence on body weight status, in adolescents. Design:Blood samples from 92 obese, 92 overweight and 92 normal weight age- and sex-matched adolescents were analysed for traditional cardiovascular disease (CVD) risk biomarkers and also total, high molecular weight (HMW), medium and low molecular weight (LMW) AN. Results:A significant inverse association was observed between total and HMW AN and waist-hip ratio (P=0.015, P=0.006, respectively), triglycerides (P=0.003, P=0.003, respectively) and systolic blood pressure (P=0.012, P=0.024, respectively) and a significant positive association with high-density lipoprotein (P<0.001, P<0.001, respectively) in multi-adjusted analyses. There was no evidence of a relationship between multimeric AN and high-sensitivity C-reactive protein. There was also little evidence of a relationship between LMW AN and CVD risk factors. There was a strong, body mass index (BMI)-independent, association between AN, CVD biomarkers and the hypertriglyceridemic waist phenotype. Conclusion:Prominent, BMI-independent associations between total and HMW AN, but not LMW AN, and CVD risk factors were already evident in this young population. This research in adolescents supports the contention that AN subfractions may have different biological actions. These associations in apparently healthy adolescents suggest an important role for AN and its subfractions in the pathogenesis of metabolic syndrome traits and indicate that the potential for total or HMW AN to act as early universal biomarkers of CV risk warrants further study.

Pioglitazone protects HDL(2&3) against oxidation in overweight and obese men

The worldwide epidemic of obesity is a major public health concern and is persuasively linked to the rising prevalence of diabetes and cardiovascular disease. Obesity is often associated with an abnormal lipoprotein profile, which may be partly negated by pioglitazone intervention, as this can influence the composition and oxidation characteristics of low-density lipoprotein (LDL). However, as pioglitazone's impact on these parameters within high-density lipoprotein (HDL), specifically HDL(2&3), is absent from the literature, this study was performed to address this shortcoming.

Genetic Markers Enhance Coronary Risk Prediction in Men: The MORGAM Prospective Cohorts

Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.

Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.

Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.

Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.

Adolescents' views about a proposed rewards intervention to promote healthy food choice in secondary school canteens

Using rewards may be an effective method to positively influence adolescent eating behaviour, but evidence regarding this approach is limited. The aim of this study was to explore young adolescent views about a proposed reward intervention associated with food choice in school canteens. Focus groups were held in 10 schools located in lower socioeconomic areas within Northern Ireland and involved 90 pupils aged 11-12 years (54 girls, 36 boys). Our findings indicated a high degree of acceptability for a reward scheme but there was major diversity in the type of rewards valued by pupils, largely defined by geographical area and socio-cultural differences. Pupils from rural areas tended to emphasize group-based and longer-term rewards, whereas pupils from urban-city schools tended to suggest individualistic and immediate rewards. The major factors influencing food choice were food price, value for money, taste and visual appearance. Pupils felt that factors outside of their control, such as being assigned to the second lunch sitting placed considerable constraints on their food choice. This research not only indicated a high degree of acceptability for a rewards-based intervention but also highlighted a number of socio-cultural and environmental factors that should be considered by researchers when developing such an intervention.

Dietary patterns and cardiovascular risk factors in adolescents and young adults: the Northern Ireland Young Hearts Project

Dietary pattern (DP) analysis allows examination of the combined effects of nutrients and foods on the markers of CVD. Very few studies have examined these relationships during adolescence or young adulthood. Traditional CVD risk biomarkers were analysed in 12-15-year-olds (n 487; Young Hearts (YH)1) and again in the same individuals at 20-25 years of age (n 487; YH3). Based on 7 d diet histories, in the present study, DP analysis was performed using a posteriori principal component analysis for the YH3 cohort and the a priori Mediterranean Diet Score (MDS) was calculated for both YH1 and YH3 cohorts. In the a posteriori DP analysis, YH3 participants adhering most closely to the 'healthy' DP were found to have lower pulse wave velocity (PWV) and homocysteine concentrations, the 'sweet tooth' DP were found to have increased LDL concentrations, systolic blood pressure, and diastolic blood pressure and decreased HDL concentrations, the 'drinker/social' DP were found to have lower LDL and homocysteine concentrations, but exhibited a trend towards a higher TAG concentration, and finally the 'Western' DP were found to have elevated homocysteine and HDL concentrations. In the a priori dietary score analysis, YH3 participants adhering most closely to the Mediterranean diet were found to exhibit a trend towards a lower PWV. MDS did not track between YH1 and YH3, and nor was there a longitudinal relationship between the change in the MDS and the change in CVD risk biomarkers. In conclusion, cross-sectional analysis revealed that some associations between DP and CVD risk biomarkers were already evident in the young adult population, namely the association between the healthy DP (and the MDS) and PWV; however, no longitudinal associations were observed between these relatively short time periods.

Young children's food brand knowledge. Early development and associations with television viewing and parent's diet

Brand knowledge is a prerequisite of children's requests and choices for branded foods. We explored the development of young children's brand knowledge of foods highly advertised on television - both healthy and less healthy. Participants were 172 children aged 3-5 years in diverse socio-economic settings, from two jurisdictions on the island of Ireland with different regulatory environments. Results indicated that food brand knowledge (i) did not differ across jurisdictions; (ii) increased significantly between 3 and 4 years; and (iii) children had significantly greater knowledge of unhealthy food brands, compared with similarly advertised healthy brands. In addition, (iv) children's healthy food brand knowledge was not related to their television viewing, their mother's education, or parent or child eating. However, (v) unhealthy brand knowledge was significantly related to all these factors, although only parent eating and children's age were independent predictors. Findings indicate that effects of food marketing for unhealthy foods take place through routes other than television advertising alone, and are present before pre-schoolers develop the concept of healthy eating. Implications are that marketing restrictions of unhealthy foods should extend beyond television advertising; and that family-focused obesity prevention programmes should begin before children are 3 years of age.