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Background: The role of glucagon-like peptide-1 receptor (GLP-1R) variants on body weight response after dietary intervention has not been evaluated so far., Objective: Our aim was to evaluate weight loss and adipocytokine levels after two hypocaloric diets with different macronutrient distribution in obese subjects with rs6923761., Design: A sample of 280 obese subjects was randomized to two hypocaloric diets., Results: 124 patients (44.3%) had the genotype GG (wild-type) and 156 (55.7%) had another genotype (mutant), i.e. GA (n = 132, 47.1%) or AA (n = 24, 8.6%). With the type I diet (low in carbohydrates) in the wild-type and mutant groups, BMI, weight, fat mass, waist circumference, insulin levels, insulin resistance and triglycerides decreased. Anthropometric parameters were higher in non-A-allele carriers than A-allele carriers. With the type II diet (low in fats) in all genotypes, BMI, weight, fat mass, waist circumference, insulin levels, total cholesterol and LDL cholesterol decreased., Conclusion: Our data showed better anthropometric parameters in obese subjects with the mutant allele (A) of the rs6923761 GLP-1R polymorphism. A lack of association of this polymorphism with weight loss or biochemical parameters after two different hypocaloric diets was observed.

Objective: The aim of our study was to investigate the role of Trp64Arg polymorphism of the beta 3-adrenergic receptor (beta 3-AR) gene on metabolic changes and weight loss secondary to a high monounsaturated fat versus a high polyunsaturated fat hypocaloric diet in obese subjects., Material and Methods: A population of 260 obese subjects was analyzed. In the basal visit, patients were randomly allocated for 3 months to either diet M (high monounsaturated fat hypocaloric diet) or diet P (high polyunsaturated fat hypocaloric diet)., Results: There were no significant differences between the positive effects (on weight, body mass index, waist circumference, fat mass) in either genotype group with both diets. With diet P and in genotype Trp64Trp, glucose levels (-6.7 ± 12.1 vs. -1.2 ± 2.2 mg/dl; p < 0.05), total cholesterol (-11.2 ± 8.1 vs. -1.0 ± 7.1 mg/dl; p < 0.05), low-density lipoprotein (LDL) cholesterol (-9.7 ± 10.1 vs. -2.2 ± 8.1 mg/dl; p < 0.05), triglycerides (-11.7 ± 13.1 vs. +1.7 ± 10.3 mg/dl; p < 0.05), homeostasis model assessment for insulin resistance (HOMA-R; -0.7 ± 1.1 vs. -0.3 ± 2.1 units; p < 0.05) and insulin levels (-1.8 ± 4.6 vs. -1.0 ± 9.1 mIU/l; p < 0.05) decreased., Conclusion: The metabolic effect of weight reduction by the two hypocaloric diets is greatest in subjects with the normal homozygous beta 3-AR gene. Improvements in total cholesterol, LDL cholesterol, triglyceride, glucose, insulin and HOMA-R levels were better than in the heterozygous group., (Copyright © 2013 S. Karger AG, Basel.)

Background: Previous studies addressing the changes of glucagon-like peptide-1 (GLP-1) concentrations in morbidly obese patients after bariatric surgery have demonstrated conflicting results. The aim of the present study was to investigate the changes in serum GLP-1 levels 9 months after biliopancreatic diversion in morbidly obese patients without diabetes mellitus., Methods: A sample of 40 morbidly obese patients without diabetes mellitus was enrolled. Biochemical and anthropometrical evaluations were conducted at basal and 9 months after surgery., Results: The mean patient age was 46.6 ± 13.1 years, and the mean preoperative body mass index (BMI) was 47.1 ± 18.1. A significant decrease in BMI, weight, waist circumference, fat mass, glucose, LDL cholesterol, total cholesterol, and triglyceride levels was observed after 9 months. Serum basal GLP-1 levels did not change after surgery (0.65 ± 0.18 ng/ml vs. 0.66 ± 0.17 ng/ml; n.s.). Postsurgical correlation analysis showed a negative association between basal GLP-1 and HDL cholesterol (r = -0.57; p < 0.01)., Conclusions: Fasting GLP-1 concentrations did not change after massive weight loss with biliopancreatic diversion in morbidly obese patients without diabetes mellitus., (Copyright © 2012 S. Karger AG, Basel.)

Objective: The aim of our study was to investigate the role of the ratio of adiponectin concentration to homeostasis model assessment insulin resistance (HOMA-IR) as a predictor of metabolic syndrome (MS) in obese subjects., Methods: We studied a population-based cross-sectional sample of 217 obese women. To estimate the prevalence of MS, the definitions of the Adult Treatment Panel III (ATP III) were considered., Results: The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve for the detection of each MS component on the basis of the ratio of the serum adiponectin concentration to HOMA-IR (A/H ratio) was higher than that for the detection based on serum adiponectin concentration (for central obesity: 0.722 vs. 0.316, for increased triglycerides: 0.579 vs. 0.500, for increased blood pressure: 0.573 vs. 0.493, and for elevated fasting plasma glucose: 0.718 vs. 0.465). The AUC of the ROC curve for the detection of MS on the basis of the A/H ratio was higher than that for the detection based on serum adiponectin concentration (0.700 vs. 0.481)., Conclusion: The A/H ratio appears to provide a discriminatory marker for MS risk and some components of MS (central obesity, increased blood pressure and elevated fasting plasma glucose) in obese women., (Copyright © 2011 S. Karger AG, Basel.)

Background: Changes in dietary intake such as underfeeding, overfeeding, as well as exercise have important effects on adipose tissue metabolism. We conducted a cross-sectional study of associations between nutrient intake and serum visfatin concentrations in a group of obese patients., Subjects: A population of 231 obese subjects was analyzed in a cross-sectional study. Biochemical analysis (basal glucose, C-reactive protein, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, blood and insulin resistance), anthropometric evaluation (weight and bioimpedance) and assessment of dietary intake were carried out., Results: The mean age was 41.8 ± 14.2 years, and the mean body mass index was 35.4 ± 5.3 among the 63 male (27.3%) and 168 female (72.7%) patients. Patients were divided into 3 groups by visfatin tertile values: group 1, <16.06 ng/ml; group 2, between 16.06 and 60.55 ng/ml; group 3, >60.55 ng/ml. Patients in group 3 had lower intakes of energy, carbohydrates, total fat, monounsaturated fat, polyunsaturated fat, saturated fat, total cholesterol and proteins than group 1. Patients in group 2 had lower intakes of energy, total fat, monounsaturated fat, saturated fat, total cholesterol and proteins than group 1. In the adjusted multivariate analysis, only monounsaturated fat intake remained as an independent predictor of visfatin levels. Visfatin concentration decreased by -3.69 ng/ml (95% CI -0.43 to -7.01) for each gram of monounsaturated fat intake., Conclusion: Monounsaturated fatty acid consumption was found to be modestly inversely associated with visfatin levels in a group of obese patients., (Copyright © 2010 S. Karger AG, Basel.)

Background: A transition of guanin to alanin at codon 54 of the fatty acid-binding protein 2 gene (FABP2) results in an amino acid substitution (Ala54 to Thr54). This polymorphism was associated with some cardiovascular risk factors., Objective: The aim of our study was to investigate the influence of the Thr54 polymorphism in the FABP2 gene on obesity anthropometric parameters and cardiovascular risk factors in the fasted state in obese subjects and the allelic distribution of this polymorphism in a geographic area of Spain., Design: A population of 264 obese subjects was analyzed in a cross-sectional study from all health centers of Castilla y Leon (Spain). A nutritional and biochemical evaluation was performed. The statistical analysis was performed for the combined Ala54/Thr54 and Thr54/Thr54 genotype as a dominant model., Results: The mean age was 41.1 ± 13.1 years and the mean BMI 36.5 ± 5.9, with 94 males (35.6%) and 170 females (74.4%). One hundred and fifty-three subjects (58%) had the genotype Ala54/Ala54 (wild-type group) and 111 (42%) participants had the genotype Ala54/Thr54 (n = 92, 34.8%) or Thr54/Thr54 (n = 19, 7.2%) (mutant-type group). The health area of Valladolid had a lower frequency of wild-type genotype and Ala54 allelic frequency than all the other health areas of Castilla y Leon. C-reactive protein was higher in the mutant-type than the wild-type group (3.4 ± 5.6 vs. 7.9 ± 10.4 mg/dl; p < 0.05)., Conclusion: The finding of this study is the association of the Thr54/Ala54 and Thr54/Thr54 FABP2 phenotypes with higher levels of C-reactive protein without relation to insulin resistance. Frequencies of this polymorphism are different among health areas of Castilla y Leon., (Copyright © 2010 S. Karger AG, Basel.)

Background and Objective: The aim of our study was to investigate the interaction between the tumor necrosis factor-α (TNF-α) gene -308G/A promoter and the leptin receptor (LEPR) gene Lys656Asn polymorphisms and their effects on serum leptin levels in obese subjects., Design: A population of 237 obese patients was analyzed prospectively. Bipolar electrical bioimpedance, a biochemical analysis and serum concentrations of leptin and TNF-α were assessed., Results: The number of subjects with both mutations was 21 (8.86%). Subjects carrying the mutant LEPR genotype had higher concentrations of leptin than those with the wild-type LEPR genotype only when they also carried the mutant TNF-α genotype (G308A or A308A) (82.7 ± 63 vs. 147.6 ± 89 ng/ml; p < 0.05). In subjects with TNF-α G308G, multivariate analysis with leptin as a dependent variable revealed fat mass as an independent predictor in the model (F = 15.4; p < 0.05), with an increase of 4.1 ng/ml (95% CI 2.5-5.6) per kilogram of fat mass. The same was seen in subjects with TNF-α G308A and A308A genotypes, with an increase in leptin levels of 3.56 ng/ml (95% CI 1.8-5.3) per kilogram fat mass., Conclusion: There is an interaction between TNF-α gene G308A promoter and LEPR gene Lys656Asn polymorphisms, with higher concentrations of leptin in the G308A and A308A genotypes combined with the mutant LEPR genotype., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To investigate the influence of the Trp64Arg polymorphism in the beta 3-adrenoreceptor gene on adipocytokines, insulin resistance and weight loss secondary to a low fat versus a low carbohydrate diet., Methods: A population of 193 obese patients was analyzed. A nutritional evaluation was performed at the beginning and at the end of a 2-month period in which subjects received 1 of 2 hypocaloric diets., Results: 172 (89.1%; 44 males, 128 females) subjects had the genotype Trp64/Trp64 (wild-type group) and 21 subjects (10.9%; 4 males, 17 females) had Trp64/Arg64 (mutant-type group). In the wild-type group BMI, weight, fat mass, waist circumference, systolic blood pressure, glucose, triglycerides, insulin, homeostasis model assessment (HOMA) and leptin decreased significantly regardless of the diet. In the mutant-type group, this was the case for BMI, weight, waist circumference, fat mass and leptin levels. Only leptin levels have a significant decrease in the wild-type group (diet I 13.7%, diet II 26.3%, p < 0.05 for both). In the mutant group, leptin decreased as well (diet I 22.5%, diet II 30.1%, p < 0.05 for both)., Conclusion: The metabolic effect of mild weight reduction by 2 hypocaloric diets is greatest in subjects homozygous for the normal beta 3-adrenoreceptor gene. Improvement in glucose, insulin and HOMA is better than in the mutant-type group., (2009 S. Karger AG, Basel.)

Background: Human obesity is characterized by high levels of leptin, and it has been suggested that obese patients may be leptin-resistant., Objective: The aim of our study was to investigate the influence of Lys656Asn polymorphism in the LEPR gene on leptin response secondary to a low fat versus a low carbohydrate diet in obese patients., Design: A population of 78 obesity patients was enrolled. Before and after 2 months of two diets, a nutritional evaluation was performed., Results: 52 patients had genotype Lys656/Lys656 (wild group) and 26 patients Lys656/Asn656 or Asn656/Asn656 (mutant group). In the low fat and wild groups, BMI, weight, fat mass, glucose, total cholesterol, triglyceride, insulin, and blood pressure decreased. In mutant type (MT), BMI, weight and fat mass decreased. In wild type (WT) with low carbohydrate diet, BMI, weight, fat mass, waist circumference, waist-to-hip ratio, total cholesterol, and blood pressures decreased. In MT, BMI, weight and fat mass decreased. Only leptin concentrations have a significant decrease in WT with both diets (diet I: 30.3%; p < 0.05) and (diet II: 15.5%; p < 0.05)., Conclusion: In WT patients, the changes in serum leptin concentration due to 2 months' intervention with low fat are higher than with a low carbohydrate diet., ((c) 2008 S. Karger AG, Basel.)

Background/aim: Obesity has multiple causes and is determined by the interaction between genetic and environmental factors. A genetic factor is a (Trp64Arg) missense mutation in the beta 3-adrenergic receptor. The aim of our study was to investigate the influence of Trp64Arg polymorphism in the beta 3-adrenergic receptor gene on weight, adipocytokines, insulin resistance, and fat distribution in obese patients., Methods: A population of 217 nondiabetic obese Caucasian outpatients was analyzed. Indirect calorimetry and tetrapolar bioimpedance results, blood pressure, nutritional intake with 3-day food records, and biochemical parameters were evaluated. The genotype of beta 3-adrenergic receptor gene polymorphism (Trp64Arg) was studied., Results: The mean age of the patients was 44.3 +/- 16.4 years, and the mean body mass index was 35.2 +/- 5.2. One hundred and eighty-six patients (52 males and 134 females; 85.8%) had the genotype Trp64/Trp64 (wild-type group), and 31 patients (11 males and 20 females; 14.2%) had the genotype Trp64/Arg64 (mutant group). In the mutant group, body mass index, weight, fat mass, waist-to-hip ratio, waist circumference, and C-reactive protein levels were higher than in the wild-type group. The adipocytokine levels were similar in both groups., Conclusion: The patients of the mutant group (Trp64/Arg64) had higher body mass index, weight, waist circumference, fat mass, waist-to-hip ratio, and C-reactive protein values than those of the wild-type group., (2008 S. Karger AG, Basel.)

Objective: Basal glucagon-like peptide-1 (GLP-1) concentrations seem to be attenuated in obese subjects, although statistical significance is unclear. Only a few studies have investigated the effect of weight reduction on GLP-1 concentrations and have found unclear results. The aim of the present study was to determine whether subjects who lose weight on a hypocaloric diet experience the same change in circulating GLP-1 levels as subjects who do not lose weight., Material and Methods: A population of 99 obese nondiabetic outpatients was analyzed in a prospective way. Weight and blood pressure were determined. Basal glucose, C-reactive protein, insulin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and basal GLP-1 blood levels were measured before and after 3 months of hypocaloric diet. Bipolar impedance examination was performed in all patients to assess body composition. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal, 52% carbohydrates, 25% lipids and 23% proteins). The exercise program consisted of aerobic exercise for at least 3 times per week (60 min each)., Results: Ninety-nine patients (20 male/79 female) gave informed consent and were enrolled in the study. Fourteen patients (2 male/12 female) did not lose weight (group I: weight increase of 2 +/- 1.1 kg, NS) and 75 patients (18 male/67 female) lost weight (group II, weight loss of 4 +/- 1.6 kg, p < 0.05). Weight, body mass index, fat mass, waist circumference, insulin, HOMA, LDL cholesterol, triglycerides and systolic blood pressure improved in group II, without significant statistical changes in group I. In group I, basal GLP-1 levels remained unchanged (7.4 +/- 3.1 vs. 7.15 +/- 3.6 ng/ml, NS). In group II, GLP-1 levels decreased significantly (8.4%, 6.88 +/- 2.5 vs. 6.3 +/- 2.4 ng/ml, p < 0.05). In the multivariate analysis with a dependent variable (levels of GLP-1 after hypocaloric diet adjusted by age and sex), only insulin levels remained as an independent predictor in the model (F = 5.9; p < 0.05), with an increase of 0.6 ng/ml (CI 95%: 0.1-1.1) in GLP-1 concentrations with each 1-mIU/ml increase of insulin., Conclusion: Hypocaloric diet decreased GLP-1 levels in patients with weight loss with a significant improvement in anthropometric parameters and cardiovascular risk factors. Nevertheless, patients without weight loss after dietary treatment exhibited unchanged GLP-1 levels. Basal insulin correlates with basal GLP-1., (Copyright 2007 S. Karger AG, Basel.)

Background: Obesity and insulin resistance are associated with cardiovascular risk factors, including altered levels of inflammatory markers and adipocytokines. The aim of the present study was to examine the relationship between circulating adipocytokines and cardiovascular risk factors., Subjects: A population of 95 obese, nondiabetic outpatients was analyzed prospectively. A complete nutritional evaluation was performed., Results: In the multivariate analysis, with leptin as a dependent variable, only fat mass remained in the model (F = 66.6; p < 0.05), with an increase of 2.24 (95% CI 1.68-2.8) ng/ml of leptin with each 1 kg of fat mass. In a new model, with adiponectin as a dependent variable, the HDL cholesterol levels remained in the model (F = 8.46; p < 0.05), with an increase of 5.38 (95% CI 1.7-9.1) ng/ml of adiponectin with each 1 mg/dl of HDL cholesterol. In a third model, with interleukin 6 (IL-6) as a dependent variable, the resistin and C-reactive protein (CRP) levels remained in the model (F = 16.8; p < 0.01), with an increase of 0.48 (95% CI 0.27-0.85) pg/ml of IL-6 with each 1 ng/ml of resistin and an increase of 0.12 (95% CI 0.029-0.214) pg/ml with each 1 mg/dl of CRP., Conclusion: Circulating adipocytokine concentrations are associated with different cardiovascular risk factors in nondiabetic obese patients., ((c) 2007 S. Karger AG, Basel.)

Background and Aims: Some studies have pointed to a role of UCP3 in the regulation of whole-body energy homeostasis and regulation of fat distribution. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on fat distribution and classical cardiovascular risk factors in obese patients., Design: A population of 225 obese patients was analyzed in a prospective way. A nutritional evaluation was performed. Dietary intake and exercise were recorded. The genotype of UCP3 gene -55CT was studied., Results: 225 patients gave informed consent and were enrolled. 178 (53 males/125 females) (79.1%) had genotype 55CC (wild group) and 47 patients (14 males/33 females) (20.9%) 55CT (mutant group). In the mutant group, resting metabolic rate was higher than in the wild group. However, resting metabolic rate corrected by fat-free mass was similar. No differences were detected in fat mass or other anthropometric parameters. C-reactive protein was higher in the mutant group than in the wild group (5.1 +/- 5.7 vs. 6.9 +/- 6.8 mg/dl; p < 0.05)., Conclusion: In the mutant group of -55CC UCP3 gene patients, C-reactive protein was higher than in the wild-type patients. However, no differences in anthropometric parameters were detected in either group., (Copyright (c) 2007 S. Karger AG, Basel.)

Background/aim: It has been found that the expression of fatty acid binding protein 2 (FABP2) mRNA is under dietary control. A G-to-A transition at codon 54 of FABP2 results in an amino acid substitution (from Ala 54 to Thr 54). This polymorphism was associated with high insulin resistance and high fasting insulin concentrations. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 protein on the response to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients., Methods: A population of 69 obese (body mass index > 30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of the lifestyle modification program, indirect calorimetry, tetrapolar electrical bioimpedance measurement, blood pressure recording, serial assessment of the nutritional intake (3 days of written food records), and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal; 52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted of aerobic exercise for at least three times/week (60 min each). Statistical analysis was performed for combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild-type Ala54/Ala54 as second group., Results: The mean age was 45.5 +/- 16.7 years, the mean body mass index was 34.1 +/- 5.1, and there were 14 males (20.3%) and 55 females (79.7%) with a weight loss of 3.17 +/- 3.5 kg (3.5%). Thirty-seven patients (53.6%) had the genotype Ala54/Ala54 (wild-type group) and 32 (46.4%) patients either the genotype Ala54/Thr54 (26 patients, 30.2%) or the genotype Thr54/Thr54 (6 patients, 16.2%). The percentage of responders (weight loss) was similar in both groups (89.2 vs. 90.6%). In the wild-type group, body mass index, weight, fat mass, low-density lipoprotein cholesterol level, and waist circumference decreased, whereas the VO2 (oxygen consumption) increased. In the mutant group, glucose, body mass index, weight, waist circumference, and systolic blood pressure decreased, and VO2 increased. No differences were detected between basal values in both groups. Only the leptin levels showed a significant decrease in the wild-type group (23.85%; p < 0.05), with no statistically significant difference in the mutant group (2.59%; NS). Resistin, tumor necrosis factor alpha, interleukin 6, insulin, and C-reactive protein remained without changes in both groups., Conclusions: Weight loss is associated with different changes, depending on the FABP2 genotype. Carriers of the Thr54 allele have a different response than wild-type obese subjects, with a significant decrease of systolic blood pressure and glucose levels in Thr54 carriers and a significant decrease in fat mass, low-density lipoprotein cholesterol, and leptin in wild-type patients., (Copyright 2006 S. Karger AG, Basel.)

Objective: The aim of our study was to determine whether energy expenditure modified by increasing body mass over the wide range of body mass index (BMI) was related to insulin resistance, cardiovascular risk factors and dietary intakes., Subjects and Methods: A population of 87 obese non-diabetic outpatients was analyzed prospectively. Indirect calorimetry, tetrapolar electrical bioimpedance, serial assessment of nutritional intake using written 3-day food records and biochemical analyses were performed., Results: The mean age was 45.1 +/- 16.7 years and the mean BMI was 35.2 +/- 5.2. Indirect calorimetry showed a resting metabolic rate (RMR) of 1,732.2 +/- 406.6 kcal/day and oxygen consumption of 266.2 +/- 63.3 ml/min. RMR corrected by fat-free mass was 36.8 +/- 14.1 kcal/day/kg. Serial assessment of nutritional intake using written 3-day food records showed a calorie intake of 1,660 +/- 551.7 cal/day, a carbohydrate intake of 168.63 +/- 76.6 g/day, a fat intake of 72.1 +/- 26.42 g/day and a protein intake of 81.1 +/- 23.3 g/day. Insulin, HOMA, systolic blood pressure, diastolic blood pressure, waist circumference, fat mass, waist-to-hip ratio were higher in the third BMI tertile than in the first and second tertiles. No differences were detected in calorie intake, carbohydrate intake, fat intake, protein intake, drinking and alcoholic habit among BMI tertiles. RMR was similar in the different tertiles and the corrected RMR by fat-free mass was higher in first tertile than in the second and third tertiles (44.2 +/- 20.7 vs. 34.5 +/- 9.1 vs. 33.1 +/- 8.5 kcal/kg/day; p < 0.05). In multivariate analysis with a dependent variable (RMR), the fat-free mass remained in the model (F = 7.8; p < 0.05), with an increase of 10.1 (95% CI 3.6-17.5) kcal/day with each 1 kg of fat-free mass adjusted by age and sex., Conclusion: Resting energy expenditure in obese patients is not related to the BMI, insulin resistance and dietary intake. RMR is related to fat-free mass in a multivariant model.