The Impact of Gender and Protein Intake on the Success of Weight Maintenance and Associated Cardiovascular Risk Benefits, Independent of the Mode of Food Provision: The DiOGenes Randomized Trial.

OBJECTIVE: Maintenance of weight loss and associated cardiovascular benefits after following energy-restricted diets is still a challenging field, and thorough investigation is needed. The present research aimed to determine the role of protein and gender in relation to two different intervention models related to food supply, in a weight maintenance trial. SUBJECTS AND METHODS: The DiOGenes trial was a long-term, multicenter, randomized, dietary intervention study, conducted in eight European countries (Clinical Trials.gov, NCT00390637), focusing on assessing the effectiveness of weight maintenance over 6 months. This secondary analysis intended to evaluate the different benefits for weight maintenance and cardiometabolic markers of two dietary advice delivery models: "shop + instruction intervention" vs "instruction-alone intervention," which were further categorized for gender and macronutrient intake. RESULTS: The weight maintenance intervention based on different macronutrient intake showed, independently of the advice delivery model, in both sexes that higher protein consumption was more effective for weight stability, showing better results in obese women (low protein: 1.65 kg in males and 0.73 Kg in females vs high protein: 1.45 kg in males and -0.93 Kg in females) . Measurements concerning cardiovascular risk markers from subjects on both structured models produced similar trends in the subsequent follow-up period, with a lower rebound in women for most of the markers analyzed. CONCLUSION: The reported dietary benefits for weight sustainability should be ascribed to the macronutrient distribution (higher protein diets) rather than to the structured mode of delivery. Higher weight regain in males was noted, as well as a metabolic divergence attributable to the sex, with a better biochemical outcome in women.

Variation in extracellular matrix genes is associated with weight regain after weight loss in a sex-specific manner.

The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we investigated whether genetic variation in ECM-related genes is associated with weight regain among participants of the European DiOGenes study. Overweight and obese subjects (n = 469, 310 females, 159 males) were on an 8-week low-calorie diet with a 6-month follow-up. Body weight was measured before and after the diet, and after follow-up. Weight maintenance scores (WMS, regained weight as percentage of lost weight) were calculated based on the weight data. Genotype data were retrieved for 2903 SNPs corresponding to 124 ECM-related genes. Regression analyses provided us with six significant SNPs associated with the WMS in males: 3 SNPs in the POSTN gene and a SNP in the LAMB1, COL23A1, and FBLN5 genes. For females, 1 SNP was found in the FN1 gene. The risk of weight regain was increased by: the C/C genotype for POSTN in a co-dominant model (OR 8.25, 95 % CI 2.85-23.88) and the T/C-C/C genotype in a dominant model (OR 4.88, 95 % CI 2.35-10.16); the A/A genotype for LAMB1 both in a co-dominant model (OR 18.43, 95 % CI 2.35-144.63) and in a recessive model (OR 16.36, 95 % CI 2.14-124.9); the G/A genotype for COL23A1 in a co-dominant model (OR 3.94, 95 % CI 1.28-12.10), or the A-allele in a dominant model (OR 2.86, 95 % CI 1.10-7.49); the A/A genotype for FBLN5 in a co-dominant model (OR 13.00, 95 % CI 1.61-104.81); and the A/A genotype for FN1 in a recessive model (OR 2.81, 95 % CI 1.40-5.63). Concluding, variants of ECM genes are associated with weight regain after weight loss in a sex-specific manner.

Body mass index in school-aged children and the risk of routinely diagnosed non-alcoholic fatty liver disease in adulthood: a prospective study based on the Copenhagen School Health Records Register.

OBJECTIVE: The relation between childhood overweight and adult non-alcoholic fatty liver disease (NAFLD) is largely unknown. We investigated if weight and weight gain in childhood increases the risk of being diagnosed with NAFLD in routine clinical settings in adulthood. PARTICIPANTS: We studied 244,464 boys and girls, born between 1930 and 1989, who attended school in Copenhagen, Denmark. Their heights and weights were measured by physicians or nurses at mandatory school health examinations at ages 7-13 years. Body mass index (BMI) z-scores were calculated from an internal age-specific and sex-specific reference. OUTCOME MEASURES: NAFLD reported in the National Patient Register and the National Register of Pathology at 18 years of age or older. HRs with 95% CIs were estimated. RESULTS: During follow-up, 1264 and 1106 NAFLD cases, respectively, occurred in men and women. In both sexes, childhood BMI z-score was not consistently associated with adult NAFLD. Change in BMI z-score between 7 and 13 years of age was positively associated with NAFLD in both sexes. When adjusted for BMI z-score at age 7 years, the HRs of adult NAFLD were 1.15 (95% CI 1.05 to 1.26) and 1.12 (95% CI 1.02 to 1.23) per 1-unit gain in BMI z-score in men and women, respectively. Associations were similar when adjusted for BMI z-score at age 13 years, and were consistent across birth years. CONCLUSIONS: A BMI gain in school-aged children is associated with adult NAFLD. Intriguingly, BMI gain appears to have an effect on adult NAFLD irrespective of either the initial or the attained BMI. Taken together, our results suggest that BMI gain in childhood, rather than the level of BMI per se, is important in the development of adult NAFLD.

Airway hyperresponsiveness and development of lung function in adolescence and adulthood.

BACKGROUND: Long-term longitudinal studies of lung function from childhood to adulthood are important in linking our understanding of childhood risk factors to adult disease. Airway hyperresponsiveness has been shown to independently affect lung function growth in studies of adolescence. The objective of the study was to test the hypothesis that airway hyperresponsiveness has an independent deleterious effect on lung function in adolescence that extends into adulthood. METHODS: A random population sample (n = 983) aged 7-17 from Copenhagen was followed longitudinally for 20 years with four examinations. RESULTS: A total of 780 (79.3%) subjects contributed with lung function measurements and bronchial provocation testing. Among these, 170 (21.8%) had airway hyperresponsiveness at one examination or more during the study period. There was no difference in initial FEV1 levels between subjects with and without airway hyperresponsiveness. In a repeated measures regression model with adjustment for asthma and smoking, airway hyperresponsiveness was independently associated with reduced rates of growth in lung function in both sexes of 23 ml/year. Reduced growth rates resulted in deficits in maximal attained level of lung function at age 18, which persisted throughout the follow-up until the last examination at age 27-37 years. CONCLUSION: Airway hyperresponsiveness has an independent deleterious effect on lung function development from 7 to 37 years resulting in a lower maximal attained lung function and persistent deficits in lung function in adulthood.

Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight.

We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (-25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene-nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies.

Body water distribution and risk of cardiovascular morbidity and mortality in a healthy population: a prospective cohort study.

BACKGROUND: Early alterations in the cardiovascular structure and function may change normal body water distribution. The resulting fluid shifts may thus serve as an early marker for cardiovascular disease. However, studies examining this in healthy populations are absent. OBJECTIVE: This study examined the association between the proportion of total body water that is extracellular water and subsequent development of non-fatal or fatal cardiovascular disease in a healthy population. METHOD: Bioelectrical impedance spectroscopy is an easy-to-use, non-invasive and relatively inexpensive technique to evaluate changes in body water distribution. A random subset (n = 2120) of Danes aged 41-71 years, examined in 1993-1994 for body water distribution by bioelectrical impedance spectroscopy was included. Cox-proportional hazard models and linear splines were performed. The ratio between resistance estimates from an infinite-frequency and from no-frequency (R∞/R0) was used as a surrogate measure of ratio between extracellular water and total body water. The outcome was 13.5 years of follow-up for cardiovascular morbidity and mortality. RESULTS: A high proportion of total body water that is extracellular water was associated with increased risk of incident cardiovascular disease. A threshold effect was evident, with greatly increased risk of cardiovascular morbidity and mortality above R∞/R0 = 0.68. Below the threshold there seemed to be no additional benefit of having a low ratio. CONCLUSION: Our findings suggest that non-clinically evident oedema, measured as an increased proportion of total body water that is extracellular, above a threshold of 0.68, may be an early marker of pre-clinical cardiovascular disease. This simple, safe, cheap and easily obtainable measure of R∞/R0 from bioelectrical impedance may help the early identification of these otherwise clinically healthy individuals who are at an increased risk of future cardiovascular disease. However, more studies are needed before it can be concluded that bioelectrical impedance spectroscopy improves clinical risk prediction.

Body mass index in childhood and adult risk of primary liver cancer.

BACKGROUND & AIMS: Childhood overweight increases the risk of early development of non-alcoholic fatty liver disease, which may predispose to carcinogenesis. We investigated if childhood body size during school ages was associated with the risk of primary liver cancer in adults. METHODS: A cohort of 285,884 boys and girls, born 1930 through 1980, who attended school in Copenhagen, were followed from 1977 to 31 December 2010. Their heights and weights were measured by school doctors or nurses at ages 7 through 13 years. Body mass index (BMI) z-scores were calculated from an internal age- and sex-specific reference. Information on liver cancer was obtained from the National Cancer Registry. Hazard ratios and 95% confidence intervals (95% CI) of liver cancer were estimated by Cox regression. RESULTS: During 6,963,105 person-years of follow-up, 438 cases of primary liver cancer were recorded. The hazard ratio (95% CI) of adult liver cancer was 1.20 (1.07-1.33) and 1.30 (1.16-1.46) per 1-unit BMI z-score at 7 years and 13 years of age, respectively. Similar associations were found in boys and girls, for hepatocellular carcinoma only, across years of birth, and after accounting for diagnoses of viral hepatitis, alcohol-related disorders, and biliary cirrhosis. CONCLUSIONS: Higher BMI in childhood increases the risk of primary liver cancer in adults. In view of the high case fatality of primary liver cancer, this result adds to the future negative health outcomes of the epidemic of childhood overweight, reinforcing the need for its prevention.

Health effect of the New Nordic Diet in adults with increased waist circumference: a 6-mo randomized controlled trial.

BACKGROUND: The regional Mediterranean Diet has been associated with lower risk of disease. OBJECTIVE: We tested the health effects of the New Nordic Diet (NND), which is a gastronomically driven regional, organic, and environmentally friendly diet, in a carefully controlled but free-living setting. DESIGN: A total of 181 centrally obese men and women, with a mean (range) age of 42 y (20-66 y), body mass index (in kg/m(2)) of 30.2 (22.6-47.3), and waist circumference of 100 cm (80-138 cm) were randomly assigned to receive either the NND (high in fruit, vegetables, whole grains, and fish) or an average Danish diet (ADD) for 26 wk. Participants received cookbooks and all foods ad libitum and free of charge by using a shop model. The primary endpoint was the weight change analyzed by both completer and intention-to-treat analyses. RESULTS: A total of 147 subjects [81% (NND 81%; ADD 82%)] completed the intervention. A high dietary compliance was achieved, with significant differences in dietary intakes between groups. The mean (±SEM) weight change was -4.7 ± 0.5 kg for the NND compared with -1.5 ± 0.5 kg for the ADD (adjusted difference: -3.2 kg; 95% CI: -4.6, -1.8 kg; P < 0.001) for the completer analysis, and the difference was -3.0 kg (95% CI: -4.0, -2.1 kg) for the intention-to-treat analysis. The NND produced greater reductions in systolic blood pressure (adjusted difference: -5.1 mm Hg; 95% CI: -8.2, -2.1 mm Hg) and diastolic blood pressure (adjusted difference: -3.2 mm Hg; 95% CI: -5.7, -0.8 mm Hg) than did the ADD. CONCLUSION: An ad libitum NND produces weight loss and blood pressure reduction in centrally obese individuals. This trial was registered at www.clinicaltrials.gov as NCT01195610.

A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations.

Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes.

Impact of weight loss and maintenance with ad libitum diets varying in protein and glycemic index content on metabolic syndrome.

OBJECTIVES: We investigated the effects of weight loss and maintenance with diets that varied with regard to protein content and glycemic index (GI) on metabolic syndrome (MetSyn) status. METHODS: Secondary analyses were performed within the Diet, Obesity and Genes (DiOGenes) study (2006-2008), a randomized controlled dietary intervention. Nine hundred and thirty-eight overweight and obese adults from eight European countries entered an 8-wk low-calorie-diet period. Seven hundred and seventy-three adults who lost at least 8% of their body weights were randomized to one of five ad libitum diets for 6 mo: 1) low-protein (LP)/low-GI (LGI); 2) LP/high-GI (HGI); 3) high-protein (HP)/LGI; 4) HP/HGI; and 5) control diet. MetSyn prevalence and a standardized MetSyn score were assessed at baseline, after the low-calorie diet, and after the intervention. RESULTS: Weight loss among participants while on the low-calorie diet significantly reduced MetSyn prevalence (33.9% versus 15.9%; P < 0.001) and MetSyn score (-1.48 versus -4.45; P < 0.001). During weight maintenance, significant changes in MetSyn score were observed between the groups, with the highest increase detected in the LP/HGI group (P = 0.039, partial η(2) = 0.023). Protein, GI, and their interaction did not have isolated effects on study outcomes. CONCLUSIONS: Neither protein nor GI affected MetSyn status in this sample of European overweight and obese adults. However, a diet with a combination of an increased protein-to-carbohydrate ratio with low-GI foods had beneficial effects on MetSyn factors.

TFAP2B -dietary protein and glycemic index interactions and weight maintenance after weight loss in the DiOGenes trial.

BACKGROUND: TFAP2B rs987237 is associated with obesity and has shown interaction with the dietary fat-to-carbohydrate ratio, which has an effect on weight loss. We investigated interactions between rs987237 and protein-to-carbohydrate ratio or glycemic index (GI) in relation to weight maintenance after weight loss. METHODS: This study included 742 obese individuals from 8 European countries who participated in the Diet, Obesity, and Genes (DiOGenes) trial, lost ≥ 8% of their initial body weight during an 8-week low-calorie diet and were randomized to one of 5 ad libitum diets with a fixed energy percentage from fat: either low-protein/low-GI, low-protein/high-GI, high-protein/low-GI, or high-protein/high-GI diets, or a control diet for a 6-month weight maintenance period. Using linear regression analyses and additive genetic models, we investigated main and dietary interaction effects of TFAP2B rs987237 in relation to weight maintenance. RESULTS: In total, 468 completers of the trial were genotyped for rs987237. High-protein diets were beneficial for weight maintenance in the AA genotype group (67% of participants), but in the AG and GG groups no differences were observed for low- or high-protein diets. On the high-protein diet, carriers of the obesity risk allele (G allele) regained 1.84 kg (95% CI: 0.02; 3.67, p = 0.047) more body weight per risk allele than individuals on a low-protein diet. There was no interaction effect between rs987237 and GI on weight maintenance. CONCLUSION: TFAP2B rs987237 and dietary protein/carbohydrate interacted to modify weight maintenance. Considering the carbohydrate proportion of the diet, the interaction was different from the previously reported rs987237-fat-to-carbohydrate ratio interaction for weight loss. Thus, TFAP2B-macronutrient interactions might diverge depending on the nutritional state.

Change in proportional protein intake in a 10-week energy-restricted low- or high-fat diet, in relation to changes in body size and metabolic factors.

OBJECTIVE: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. METHODS: Obese adults (n = 771) were randomised to a 600 kcal energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (<-2 /-2 to 2/>2) on outcomes. RESULTS: The low-fat group with >2 prot% increase lost 1.1 kg more weight (p = 0.03) and reduced cholesterol by 0.25 mmol/l more (p = 0.003) than the high-fat group with >2 prot% decrease. These differences were 2.5-fold and 1.8-fold greater than the differences between the low-fat and high-fat groups while not considering prot% change. The high-fat group reduced plasma triglycerides more than the low-fat group, but not compared to those in the low-fat group with >2 units prot% increase (p fat-protein interaction = 0.01). CONCLUSIONS: Under energy restriction, participants on a low-fat diet who had increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet.

The influence of early exposure to vitamin D for development of diseases later in life.

BACKGROUND: Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied. The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood. METHODS/DESIGN: The study is based on the fact that in 1961 fortifying margarine with vitamin D became mandatory in Denmark and in 1972 low fat milk fortification was allowed. Apart from determining the influences of exposure prior to conception and during prenatal life, we will examine the importance of vitamin D exposure during specific seasons and trimesters, by comparing disease incidence among individuals born before and after fortification. The Danish National databases assure that there are a sufficient number of individuals to verify any vitamin D effects during different gestation phases. Additionally, a validated method will be used to determine neonatal vitamin D status using stored dried blood spots (DBS) from individuals who developed the aforementioned disease entities as adults and their time and gender-matched controls. DISCUSSION: The results of the study will contribute to our current understanding of the significance of supplementation with vitamin D. More specifically, they will enable new research in related fields, including interventional research designed to assess supplementation needs for different subgroups of pregnant women. Also, other health outcomes can subsequently be studied to generate multiple health research opportunities involving vitamin D. Finally, the results of the study will justify the debate of Danish health authorities whether to resume vitamin D supplementation policies.

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

Chronic family stress moderates the association between a TOMM40 variant and triglyceride levels in two independent Caucasian samples.

TOMM40 SNP rs157580 has been associated with triglyceride levels in genome-wide association studies (GWAS). Chronic caregiving stress moderates the association between triglyceride levels and a nearby SNP rs439401 that is associated with triglyceride levels in GWAS. Here, we report data from two independent Caucasian samples (242 U.S. women and men; 466 Danish men) testing the hypothesis that chronic family stress also moderates the association between rs157580 and triglyceride levels. The interaction of rs157580 and family stress in predicting triglyceride levels was statistically significant in the U.S. sample (p=0.004) and marginally significant (p=0.075) in the Danish sample. The G allele of rs157580 was associated with increased triglyceride levels among family stressed cases in both samples compared with A/A cases, but not among controls. Chronic family stress moderates the association of rs157580 variants with triglyceride levels and should be taken into account for disease risk assessment and potential intervention.

Influence of SNPs in nutrient-sensitive candidate genes and gene-diet interactions on blood lipids: the DiOGenes study.

Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene-diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP-diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect) ,and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP-dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of 20.26 mmol/l per A-allele/protein unit (95% CI 20.38, 20.14, P=0.000043). In conclusion, we investigated SNP-diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.

A multicentre weight loss study using a low-calorie diet over 8 weeks: regional differences in efficacy across eight European cities.

PRINCIPLES: The efficacy of low-calorie diets (LCDs) has not been investigated in large-scale studies or among people from different regions, who are perhaps unaccustomed to such methods of losing weight. The aim of the present study was to investigate changes in obesity measures among overweight/obese adults from eight European cities (from Northern, Central and Southern Europe) during the 8-week LCD phase of the DiOGenes study (2006-2007), a family-based, randomised, controlled dietary intervention. METHODS: 938 overweight/obese adults completed baseline examinations and underwent an 8-week LCD, providing 3.3-4.2 MJ/day to replace all meals. Anthropometric measurements and body composition were assessed at baseline and post-LCD. RESULTS: 773 (82.4%) adults (mean age, 43.1 y) completed the LCD successfully. The highest drop-out rate was observed in Southern (24.9%) and the lowest in Northern (13.3%) European cities. Overall, the LCD induced favourable changes in all outcomes, including an approximate 11.0% reduction in body weight and body fat percentage. Changes in outcomes differed significantly between regions, with North- and Central-European cities generally achieving higher percentage reductions in most anthropometric measurements assessed. Nonetheless, participants in Southern Europe reduced their body fat percentage significantly more than participants in Northern Europe (-11.8 vs. -9.5%, P = 0.017). CONCLUSIONS: The LCD significantly improved anthropometric and body composition measurements in all cities participating in DiOGenes.

Cognitive and weight-related correlates of flexible and rigid restrained eating behaviour.

OBJECTIVES: Examine the association between components of restrained eating, cognitive performance and weight loss maintenance. METHODS: 106 women, all members of a commercial slimming organisation for at least 6 months (mean±SD: 15.7±12.4 months), were studied who, having lost 10.1±9.7 kg of their initial weight, were hoping to sustain their weight loss during the 6 month study. Dietary restraint subcomponents flexible and rigid restraint, as well as preoccupying cognitions with food, body-shape and diet were assessed using questionnaires. Attentional bias to food and shape-related stimuli was measured using a modified Stroop test. Working memory performance was assessed using the N-back test. These factors, and participant weight, were measured twice at 6 month intervals. RESULTS: Rigid restraint was associated with attentional bias to food and shape-related stimuli (r=0.43, p<0.001 resp. r=0.49, p<0.001) whereas flexible restraint correlated with impaired working memory (r=-0.25, p<0.05). In a multiple regression analyses, flexible restraint was associated with more weight lost and better weight loss maintenance, while rigid restraint was associated with less weight loss. CONCLUSIONS: Rigid restraint correlates with a range of preoccupying cognitions and attentional bias to food and shape-related stimuli. Flexible restraint, despite the impaired working memory performance, predicts better long-term weight loss. Explicitly encouraging flexible restraint may be important in preventing and treating obesity.

Determinants of human adipose tissue gene expression: impact of diet, sex, metabolic status, and cis genetic regulation.

Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently controlled AT gene expression. These analyses help understanding the relative importance of environmental and individual factors that control the expression of human AT genes and therefore may foster strategies aimed at improving AT function in metabolic diseases.

TFAP2B influences the effect of dietary fat on weight loss under energy restriction.

BACKGROUND: Numerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction. METHODS AND FINDINGS: Randomized controlled trial of 771 obese adults. ( REGISTRATION: ISRCTN25867281.) One SNP was selected for replication in another weight loss intervention study of 934 obese adults. The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat (fat%) in range of 20-25 or 40-45. The replication study used an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for estimation of interaction effects. The main outcomes were intervention weight loss and waist reduction. In the trial, mean change in fat% intake was -12/+4 in the low/high-fat groups. In the replication study, it was -23/-12 among those reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was associated with 1.0 kg (95% CI, 0.4; 1.6) greater weight loss on the low-fat, and GG genotype with 2.6 kg (1.1; 4.1) greater weight loss on the high-fat (interaction p-value; p = 0.00007). The replication study showed a similar (non-significant) interaction pattern. Waist reduction results generally were similar. Study-strengths include (i) the discovery study randomised trial design combined with the replication opportunity (ii) the strict dietary intake control in both studies (iii) the large sample sizes of both studies. Limitations are (i) the low minor allele frequency of the TFAP2B polymorphism, making it hard to investigate non-additive genetic effects (ii) the different interventions preventing identical replication-discovery study designs (iii) some missing data for non-completers and dietary intake. No adverse effects/outcomes or side-effects were observed. CONCLUSIONS: Under energy restriction, TFAP2B may modify the effect of dietary fat intake on weight loss and waist reduction.