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Hooton H.,French Institute of Health and Medical Research | Hooton H.,University Pierre and Marie Curie | Hooton H.,University of Paris Descartes | Angquist L.,Copenhagen University | And 30 more authors.
PLoS ONE | Year: 2012

Background/Aims:Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology-this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors-increased by high protein, glycemic index and energy diets.Methods:Four tag SNPs (rs7511673, rs11576175, rs10888390 and rs1136774) were selected to capture all common variation in the CTSS region. Association between these four SNPs and several adiposity measurements (BMI, waist circumference, waist for given BMI and being a weight gainer-experiencing the greatest degree of unexplained annual weight gain during follow-up or not) given, where applicable, both as baseline values and gain during the study period (6-8 years) were tested in 11,091 European individuals (linear or logistic regression models). We also examined the interaction between the CTSS variants and dietary factors-energy density, protein content (in grams or in % of total energy intake) and glycemic index-on these four adiposity phenotypes.Results:We found several associations between CTSS polymorphisms and anthropometric traits including baseline BMI (rs11576175 (SNP N°2), p = 0.02, β = -0.2446), and waist change over time (rs7511673 (SNP N°1), p = 0.01, β = -0.0433 and rs10888390 (SNP N°3), p = 0.04, β = -0.0342). In interaction with the percentage of proteins contained in the diet, rs11576175 (SNP N°2) was also associated with the risk of being a weight gainer (pinteraction = 0.01, OR = 1.0526)-the risk of being a weight gainer increased with the percentage of proteins contained in the diet.Conclusion:CTSS variants seem to be nominally associated to obesity related traits and this association may be modified by dietary protein intake. © 2012 Hooton et al.


Halkjaer J.,Danish Cancer Society | Olsen A.,Danish Cancer Society | Overvad K.,University of Aarhus | Overvad K.,Aarhus University Hospital | And 14 more authors.
International Journal of Obesity | Year: 2011

Background:As protein is considered to increase thermogenesis and satiety more than other macronutrients, it may have beneficial effects on prevention of weight gain and weight maintenance.Objective:The objective of this study is to assess the association between the amount and type of dietary protein, and subsequent changes in weight and waist circumference (WC).Methods:89 432 men and women from five countries participating in European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a mean of 6.5 years. Associations between the intake of protein or subgroups of protein (from animal and plant sources) and changes in weight (g per year) or WC (cm per year) were investigated using gender and centre-specific multiple regression analyses. Adjustments were made for other baseline dietary factors, baseline anthropometrics, demographic and lifestyle factors and follow-up time. We used random effect meta-analyses to obtain pooled estimates across centres.Results:Higher intake of total protein, and protein from animal sources was associated with subsequent weight gain for both genders, strongest among women, and the association was mainly attributable to protein from red and processed meat and poultry rather than from fish and dairy sources. There was no overall association between intake of plant protein and subsequent changes in weight. No clear overall associations between intakes of total protein or any of the subgroups and changes in WC were present. The associations showed some heterogeneity between centres, but pooling of estimates was still considered justified.Conclusion:A high intake of protein was not found associated with lower weight or waist gain in this observational study. In contrast, protein from food items of animal origin, especially meat and poultry, seemed to be positively associated with long-term weight gain. There were no clear associations for waist changes. © 2011 Macmillan Publishers Limited All rights reserved.


Du H.,National Institute for Public Health and the Environment RIVM | Du H.,Nutrition and Toxicology Research Institute of Maastricht NUTRIM | Vimaleswaran K.S.,Institute of Metabolic Science | Angquist L.,Copenhagen University | And 18 more authors.
PLoS ONE | Year: 2011

Background: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. Aim: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake. Methods and Findings: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2×10-7). Conclusions: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation. © 2011 Du et al.


Romaguera D.,Imperial College London | Angquist L.,Copenhagen University | Du H.,National Institute for Public Health and the Environment RIVM | Du H.,Nutrition and Toxicology Research Institute of Maastricht NUTRIM | And 15 more authors.
PLoS ONE | Year: 2011

Background: Dietary factors such as low energy density and low glycemic index were associated with a lower gain in abdominal adiposity. A better understanding of which food groups/items contribute to these associations is necessary. Objective: To ascertain the association of food groups/items consumption on prospective annual changes in "waist circumference for a given BMI" (WC BMI), a proxy for abdominal adiposity. Design: We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WC BMI was defined as the residuals of waist circumference regressed on BMI, and annual change in WC BMI (ΔWC BMI, cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between food groups/items and ΔWC BMI was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates. Results: Higher fruit and dairy products consumption was associated with a lower gain in WC BMI whereas the consumption of white bread, processed meat, margarine, and soft drinks was positively associated with ΔWC BMI. When these six food groups/items were analyzed in combination using a summary score, those in the highest quartile of the score - indicating a more favourable dietary pattern -showed a ΔWC BMI of -0.11 (95% CI -0.09 to -0.14) cm/y compared to those in the lowest quartile. Conclusion: A dietary pattern high in fruit and dairy and low in white bread, processed meat, margarine, and soft drinks may help to prevent abdominal fat accumulation. © 2011 Romaguera et al.


Vimaleswaran K.S.,Institute of Metabolic Science | Angquist L.,Copenhagen University | Hansen R.D.,Danish Cancer Society | Van Der A. D.L.,National Institute for Public Health and the Environment RIVM | And 17 more authors.
Obesity | Year: 2012

Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6.8 years follow-up in a large-scale prospective study and examined whether these associations were modified by dietary energy percentage from fat, protein, carbohydrate, or glycemic index (GI). This study comprised data from five countries of European Prospective Investigation into Cancer and Nutrition (EPIC) and was designed as a case-cohort study for weight gain. Analyses included 11,091 individuals, of whom 5,584 were cases (age (SD), 47.6 (7.5) years), defined as those with the greatest unexplained annual weight gain during follow-up and 5,507 were noncases (48.0 (7.3) years), who were compared in our case-noncase (CNC) analyses. Furthermore, 6,566 individuals (47.9 (7.3) years) selected from the total sample (all noncases and 1,059 cases) formed the random subcohort (RSC), used for continuous trait analyses. Interactions were tested by including interaction terms in the models. In the RSC-analyses, FTO-rs9939609 was associated with BMI (Β (SE), 0.17 (0.08) kgm2/allele; P = 0.034) and WC (0.47 (0.21) cm/allele; P = 0.026) at baseline, but not with weight change (5.55 (12.5) gyear-1/allele; P = 0.66) during follow up. In the CNC-analysis, FTO-rs9939609 was associated with increased risk of being a weight-gainer (OR: 1.1; P = 0.045). We observed no interaction between FTO-rs9939609 and dietary fat, protein and carbohydrate, and GI on BMI and WC at baseline or on change in weight and WC. FTO-rs9939609 is associated with BMI and WC at baseline, but association with weight gain is weak and only observed for extreme gain. Dietary factors did not influence the associations. © 2011 The Obesity Society.


Romaguera D.,Imperial College London | Angquist L.,Copenhagen University | Du H.,National Institute for Public Health and the Environment RIVM | Du H.,Nutrition and Toxicology Research Institute of Maastricht NUTRIM | And 15 more authors.
PLoS ONE | Year: 2010

Background: Given the recognized health effects of visceral fat, the understanding of how diet can modulate changes in the phenotype "waist circumference for a given body mass index (WCBMI)", a proxy measure of visceral adiposity, is deemed necessary. Hence, the objective of the present study was to assess the association between dietary factors and prospective changes in visceral adiposity as measured by changes in the phenotype WCBMI. Methods and Findings: We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WCBMI was defined as the residuals of waist circumference regressed on body mass index, and annual change in WCBMI (ΔWCBMI, cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between energy, energy density (ED), macronutrients, alcohol, glycemic index (GI), glycemic load (GL), fibre and ΔWCBMI was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates. Men and women with higher ED and GI diets showed significant increases in their WCBMI, compared to those with lower ED and GI [1 kcal/g greater ED predicted a ΔWCBMI of 0.09 cm (95% CI 0.05 to 0.13) in men and 0.15 cm (95% CI 0.09 to 0.21) in women; 10 units greater GI predicted a ΔWCBMI of 0.07 cm (95% CI 0.03 to 0.12) in men and 0.06 cm (95% CI 0.03 to 0.10) in women]. Among women, lower fibre intake, higher GL, and higher alcohol consumption also predicted a higher DWCBMI. Conclusions: Results of this study suggest that a diet with low GI and ED may prevent visceral adiposity, defined as the prospective changes in WCBMI. Additional effects may be obtained among women of low alcohol, low GL, and high fibre intake. © 2010 Romaguera et al.


Du H.,University of Oxford | Du H.,National Institute for Public Health and the Environment RIVM | Du H.,Nutrition and Toxicology Research Institute of Maastricht NUTRIM | Eskens E.,Wageningen University
Acta Cardiologica | Year: 2010

Obesity has become a serious public health problem worldwide, and dietary composition can play a role in its prevention and treatment. However, available literature on the impacts of different dietary factors on weight change is inconsistent, or even conflicting. In this review, we briefly summarized the mechanisms and influences of several major dietary determinants of weight change, with a focus on their potential in the prevention of weight gain or regain.We discussed the intake of fat, protein, total carbohydrates, fruits and vegetables, fibre, free sugars, fructose and sugar sweetened beverages, dietary energy density, portion size, eating outside home, glycaemic index and glycaemic load. Popular weight loss diets, including the Atkins diet,Weight Watchers, Ornish diet and Zone diet, are also briefly discussed for their safety and efficacy in the maintenance of weight loss.

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