Martin Forejt

No association of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin gene with food preferences in the Czech population.

Abstract Background: Previously, it has been reported that mutations in the genes encoding for adipokines may be associated with impaired food intake and may serve as potential obesity biomarkers. The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes. Patients and Methods: Using PCR followed by restriction analysis, we studied 185 volunteers. Basic anthropometrical characteristics associated to obesity were measured and the food intake was monitored using a 7-day record method. In the group of obese individuals, a subset of 34 morbidly obese patients was studied for plasma leptin and soluble leptin receptor levels. Results: None of the examined polymorphisms was associated to anthropometrical or demographic characteristics of the study subjects. The Gln223Arg polymorphism within the leptin receptor gene was significantly associated with lower plasma leptin levels (the RR genotype being more frequent in patients with lower plasma leptin levels; P = 0.001). No associations of the examined polymorphisms with food preferences was observed. Conclusions: Based on our results, the examined polymorphisms in the adipokine genes do not seem to be the major risk factor for obesity development in the Czech population nor significantly affect food preferences.

Genotype x nutrient association of common polymorphisms in obesity-related genes with food preferences and time structure of energy intake.

Personal food preferences can either enhance or suppress the development of obesity and the selection and proportion of macronutrients in the diet seem to have a heritable component. In the present study, we therefore focused on dietary composition as a specific trait related to obesity and we determined whether genetic variations in leptin (LEP), LEP receptor (LEPR), adiponectin (ADIPOQ), IL-6 and pro-opiomelanocortin (POMC) underlie specific native food preferences and obesity-related anthropometric parameters. The total of 409 individuals of Czech Caucasian origin were enrolled into the present study and 7 d food records were obtained from the study subjects along with selected anthropometric measurements. In a subset of study subjects, plasma levels of ADIPOQ, LEP and soluble LEPR were measured. Independently of the BMI of the individuals, common variations in LEP and LEPR genes were associated with specific eating patterns, mainly with respect to timing of eating. The LEP + 19A/G polymorphism served as an independent predictor for BMI, percentage of body fat and skinfold thickness and significantly affected the time structure of the daily energy intake. The POMC RsaI polymorphism was associated with percentage of body fat. The ADIPOQ 45 T/G polymorphism was associated with the thickness of the subscapular skinfold. The LEPR Gln223Arg polymorphism was associated with multiple parameters, including diastolic blood pressure, meal sizes during the day and plasma ADIPOQ levels. In a separate analysis, soluble leptin receptor (sObR) plasma levels and LEP:sObR ratio were significantly correlated with systolic blood pressure (beta = - 0.66, P = 0.002; beta = - 1.23, P = 0.02) and sObR plasma levels also served as an independent predictor for diastolic blood pressure (beta = - 0.50; P = 0.04). To conclude, we report common allelic variants associated with specific feeding behaviour and obesity-related anthropometric traits. Moreover, we identified allelic variants that significantly influence the time structure of food intake during the day.

The prediction role of indexes of circulating adipokines for common anthropometric and nutritional characteristics of obesity in the obese Central European population.

AIMS This study was designed to investigate the relationship between 8 selected adipokines (leptin, leptin receptor, adiponectin, agouti-related peptide, omentin, visfatin, adipsin and resistin), dietary composition and anthropometric parameters found in the Central European obese population. METHODS A total of 65 unrelated obese Central European Caucasian individuals were recruited for the study. Phenotypic measurements included weight, height, BMI, lean body mass, fat mass, body fat, waist and hip circumference, waist-hip ratio (WHR) and skinfold thickness. Participants completed standardized self-reported 7-day food records. Plasma levels of leptin, leptin receptor, adiponectin, agouti-related peptide (AgRP), resistin, adipsin, omentin and visfatin were examined using ELISA. RESULTS Multiple associations (weight, height, percentage of body fat, waist circumference, hip circumference, WHR and sum of skinfold thickness) with the circulation levels of the investigated adipokines were identified. Leptin-Leptin receptor (L-LR) levels were found to correlate with total energy intake and macronutrients while adipsin was found to strongly correlate with multiple adipokines. Furthermore, the L-LR index was found to constitute a more accurate description of the relationship between BMI and body weight than individual measurements and the Ag-LR index was found to strongly correlate with both anthropometric and dietary characteristics. CONCLUSION Following confirmation on larger population samples and on samples of different ethnicities, the reported adipokine indexes could become a useful tool for estimating nutritional status and predicting the body composition of specific patient groups.

The common polymorphism Val109Asp in the omentin gene is associated with daily energy intake in the Central-European population

Abstract Background Omentin is an adipokine expressed predominantly in visceral adipose tissue, with adipose tissue stromal cells being the main source. Very little is known about the relationship between the genetic variability of the omentin gene and pathophysiology of obesity, although omentin is believed to play an important role in visceral obesity development. The aim of the study was to investigate two common polymorphisms in the omentin gene (rs2274908 and rs2274907) and dietary composition and anthropometric parameters of obesity in the Central European population. Material and methods A total of 495 subjects were included into the study, they were further dividend into the non-obese, obese, and morbidly obese cohorts. Dietary habits were established using the 7-day food records and selected anthropometric parameters were measured. Results There were significant differences in genotype distributions of rs2274907 between the obese and morbidly obese cohorts (P = 0.01). In the multivariate modelling, the rs2274907 polymorphism expressed independent prediction role for the daily energy intake, independently on the age and gender (P = 0.03); the TT genotype associated with the lowest (7877 ± 2780 J/day) and the AA genotype with the highest (8764 ± 2467 J/day) average energy intake. The rs2274907 also significantly associated with the daily consumption of fat and proteins. Conclusion This is, so far, the first study to investigate the polymorphisms in the omentin gene in a large population cohort of obese and non-obese individuals. Based on our results, the rs2274907 polymorphism is associated with the daily energy intake as well as daily intake of fat and protein.

Association of genetic variability in selected regions in visfatin (NAMPT) gene with anthropometric parameters and dietary composition in obese and non-obese Central-European population

AIMS Visfatin (NAMPT/PBEF) is a recently identified adipocytokine which harbors strong insulin-mimetic activity and was reported to be associated with obesity. However, nothing is known about whether visfatin is related to specific nutritional behavior which may result in obesity development. This is the first study focusing on genetic variability of the visfatin gene and its association with circulating visfatin, anthropometric parameters and dietary composition. MATERIALS AND METHODS We analyzed a total of 11 exons and adjacent non-coding regions of the NAMPT gene in 20 extremely obese Czech individuals (mean BMI 52.2±5.0 SD) using direct sequencing and a frequency of rs2302559 was established in the validation cohort of another 605 individuals with completed 7-day food records and complex anthropometric measurements. Serum levels of visfatin, leptin and leptin-receptor were measured in all sequenced individuals and in part of the validation cohort. RESULTS Three common polymorphisms were identified, two in non-coding regions (rs78411774 A/C, rs71564769 A/C) and one synonymous SNP in exon 7 (rs2302559 A/G). The rs2302559 showed significant correlation with visfatin serum level throughout the entire study cohort (p<0.001); there was a significant tendency toward higher visfatin levels in G allele carriers with GG homozygotes having the highest visfatin serum levels. Furthermore, a negative correlation was observed between visfatin and leptin serum level (p=0.01). No association between investigated SNPs and anthropometric parameters or native dietary composition was observed. CONCLUSION This is the first study to demonstrate that the rs2302559 polymorphism in the PBEF gene is related to circulating levels of visfatin. As the SNP is synonymous, we hypothesize it might be linked to another SNP in the PBEF gene which controls visfatin serum levels.

B-cell activating factor (BAFF) – a new factor linking immunity to diet?

B cell activation factor (BAFF) is a recently discovered member of the TNF ligand superfamily secreted by adipocytes, previously linked to autoimmune and lymphoproliferative disease. The aim of this study was to investigate the relationship between BAFF plasma levels and the non-modified, usual dietary composition as well as obesity-related anthropometric parameters in a cohort of 58 obese and non-obese Central-European Caucasian individuals. We found that BAFF had an independent predictive role for percentage of body fat; moreover, BAFF levels were correlated with waist and hip circumference. BAFF plasma levels were also significantly correlated with investigated dietary composition based on the 7-day food records, as the BAFF levels correlated with the percentage of energy derived from the carbohydrates and with energy derived from the dietary fat. Our results suggest that BAFF may play a role in linking the immune status and metabolic response to diet.

The PER3 VNTR polymorphism is a predictor of dietary composition in the Central European population

Objectives, design: The aim of this case control study was to investigate possible associations of the variable number tandem-repeat (VNTR) polymorphism in the PER3 gene with obesity-related anthropometric traits, sleep and nutritional behaviour. Setting: A total of 329 volunteers of the Czech Caucasian origin were enrolled in the study. The allele-specific PCR-based method was used to determine the VNTR PER3 genotypes, dietary composition and time patterns were evaluated using seven day native food records and seven day sleep records. Results: No differences were observed in allele frequencies between the obese and the non-obese individuals. The PER3 VNTR polymorphism was associated with the total daily energy derived from carbohydrates (p < 0.01) and fat (p < 0.02). No association with sleep homeostasis was observed. Conclusions: We have demonstrated the relationship between the PER3 VNTR polymorphism and behavioural patterns of the food intake in the Central-European population.

Variability in CNR1 locus influences protein intake and smoking status in the Central-European population

Abstract Objectives The endocannabinoid receptor 1 (CB1) is encoded by the CNR1 gene and has been recently recognized to play an important role in the regulation of satiety and feeding behaviour with a huge potential of modulating metabolic response and feeding control. The aim of the study was to investigate the potential of three selected single nucleotide polymorphisms (SNPs) in the CNR1 locus on native dietary composition in the Central-European Caucasian population. Methods A total of 258 unrelated individuals originating from the Central-European Caucasian population were enrolled into the study and rs1049353, rs12720071, and rs806368 polymorphisms in CNR1 locus were examined in these individuals using PCR-based methodology. Body composition was assessed using a bioimpedance method, various anthropometric parameters were investigated (waist and hip circumference, skin folds), and native dietary composition was analysed using 7-day food records as well as a food frequency questionnaire. Results Allelic variations and common haplotypes in the CNR1 gene were associated with the daily intake of proteins, fluids, and fibre, regardless of the physical activity of the individuals. The common haplotype in the CNR1 gene was associated with self-reported smoking (number of cigarettes per day, smoking years). Discussion Our results indicate that specific genetic variations in the CNR1 gene may act as susceptibility markers for specific dietary composition in the Central-European population.

Relation between adiponectin 45 T/G polymorphism and dietary composition in the Czech population

In this study on 138 Czech Caucasians, the ADIPOQ 45T/G polymorphism was associated with the dietary composition. As the GG homozygotes were associated with the increased intake of carbohydrates, we suggest that a proportion of the prodiabetogenic effect of the polymorphism might be due to its influence on eating behaviour.

Higher Energy Intake Variability as Predisposition to Obesity: Novel Approach Using Interquartile Range

OBJECTIVE It is known that total energy intake and its distribution during the day influences human anthropometric characteristics. However, possible association between variability in total energy intake and obesity has thus far remained unexamined. This study was designed to establish the influence of energy intake variability of each daily meal on the anthropometric characteristics of obesity. METHODS A total of 521 individuals of Czech Caucasian origin aged 16–73 years (390 women and 131 men) were included in the study, 7-day food records were completed by all study subjects and selected anthropometric characteristics were measured. The interquartile range (IQR) of energy intake was assessed individually for each meal of the day (as a marker of energy intake variability) and subsequently correlated with body mass index (BMI), body fat percentage (%BF), waist-hip ratio (WHR), and waist circumference (cW). RESULTS Four distinct models were created using multiple logistic regression analysis and backward stepwise logistic regression. The most precise results, based on the area under the curve (AUC), were observed in case of the %BF model (AUC=0.895) and cW model (AUC=0.839). According to the %BF model, age (p<0.001) and IQR-lunch (p<0.05) seem to play an important prediction role for obesity. Likewise, according to the cW model, age (p<0.001), IQR-breakfast (p<0.05) and IQR-dinner (p <0.05) predispose patients to the development of obesity. The results of our study show that higher variability in the energy intake of key daily meals may increase the likelihood of obesity development. CONCLUSIONS Based on the obtained results, it is necessary to emphasize the regularity in meals intake for maintaining proper body composition.