Development of a Nutrigenetic Test for Personalized Prescription of Body Weight Loss Diets (Obekit) (Obekit)

This study evaluates the relationship between several genetic variants and the response to a hypocaloric diet, in order to design a genetic test which permits prescribe the more personalized diet for each individual according to her genotype. Half of the participants will assigned to a moderate high protein diet, while the other half will assigned to a high carbohydrate diet.

Obesity has reached epidemic proportions becoming a major global public health challenge since it is associated with an increased risk of type 2 diabetes, cardiovascular disease, stroke, arthritis and some forms of cancer. Therefore, a large number of strategies have been investigated in order to induce a negative energy balance and consequently body weight loss mainly inducing a low calorie diet and sometimes accompanied by an increase in physical activity. However, individual responses to body weight loss interventions vary widely and several studies have aimed to identify psychological, behavioral and personal predictors of this variability. In this context, the hypothesis of the present study is that part of the interindividual variability in relation to the success of certain weight loss treatments is based on gene-diet interactions. Depending on the composition of the diet and the genotype of each individual, it is more or less easy to reduce and maintenance body weight. After the recruitment and selection of the study participants, the study will consists of a 4-month hypocaloric diet ("body weight loss period") followed by a second 6-month period ("body weight maintenance period") in which the subjects of the study will continue with the diet, but without any energy restriction. The participants will assigned to one of the two hypocaloric diets (-30% of the studied requirements for each individual) with different macronutrient composition: Moderately high protein diet: 40% of the energy derived from carbohydrates, 30% of the energy derived from protein and 30% of the energy derived from fat. Low fat diet: 60% of the energy derived from carbohydrates, 30% of the energy derived from protein and 30% of the energy derived from fat. A group of normal weight individuals (n 12) will be recruited in order to compare the different parameters obtained in the obese subjects with those of normal population. They will be not subjected to any intervention.

Genetics, Polymorphism, Epigenetics, Metagenomics, Metabolomics, Metabolic syndrome conditions, Precision nutrition

Caloric restriction (-30% total energy intake) Macronutrient distribution: 40% of the energy derived from carbohydrates, 30% of the energy derived from protein and 30% of the energy derived from fat

Caloric restriction (-30% total energy intake) Macronutrient distribution: 60% of the energy derived from carbohydrates, 18% of the energy derived from protein and 22% of the energy derived from fat

After the recruitment randomization of the study participants, the study will consists of a 4-month nutritional intervention ("body weight loss period") followed by a second 6-month period ("body weight maintenance period") in which the subjects of the study will continue with the assigned diet, but without any energy restriction.

After the recruitment randomization of the study participants, the study will consists of a 4-month nutritional intervention ("body weight loss period") followed by a second 6-month period ("body weight maintenance period") in which the subjects of the study will continue with the assigned diet, but without any energy restriction.the energy derived from fat

Waist and hip circumferences will be measured with a tape measure at baseline and at the end of the body weight loss period (16 weeks)

Waist and hip circumferences will be measured with a tape measure at the end of the body weight loss period (16 weeks) and at the end of the body weight maintenance period (40 Weeks)

Fat mass will be measured by bioelectric bioimpedance and Dual X-ray absorptiometry at baseline and at the end of the body weight loss period (16 Weeks)

Fat mass will be measured by bioelectric bioimpedance and Dual X-ray absorptiometry at the end of the body weight loss period (16 weeks) and at the end of the body weight maintenance period (40 Weeks)

Single nucleotide polymorphisms will be measured from Genomic DNA from oral epithelial cells (collected in ORAcollect DNA, DNAGenotek) and from peripheral blood mononuclear cells (PBMC) by using massive sequencing in a Ion Torrent sequencer

DNA methylation levels will be measured in PBMC by Microarray (Illumina. 450k methylation array) and validation specific sites by Sequenom (MassArray) and Methylationsensitive High-Resolution Melting (MS-HRM) (Real Time PCR) at baseline and at the end of the body weight loss period (16 Weeks)

DNA methylation levels will be measured in PBMC by Microarray (Illumina 450k methylation array) and validation specific sites by Sequenom (MassArray) and MS-HRM (Real Time PCR) at the end of the body weight loss period (16 weeks) and at the end of the maintenance body weight period (40 Weeks)

Metabolic profiling will be measured in urine by High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) at baseline and at the end of the body weight loss period (16 Weeks)

Metabolomic profile will be measured in urine by HPLC-MS at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Lipidomic profile will be measured in plasma by HPLC-MS at baseline and at the end of the body weight loss period (16 Weeks)

Lipidomic profile will be measured in plasma by HPLC-MS at the end of the body weight loss period (16 weeks) and at the end of the body weight maintenance period (40 Weeks)

Proteomic profile will be measured in plasma by Two-Dimensional Fluorescence Difference Gel Electrophoresis (2D-DIGE) and Liquid Chromatography Electrospray Ionization with Tandem Mass Spectrometry (LC-ESI-MS/MS) at baseline and at the end of the body weight loss period (16 Weeks)

Proteomic profile will be measured in plasma by 2D-DIGE and LC-ESI-MS/MS at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Gut microbiota composition will be measured by Pyrosequencing 16SR RNA at baseline and at the end of the body weight loss period (16 Weeks)

Gut microbiota composition will be measured by Pyrosequencing 16SR RNA at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

mRNA expression will be measured by GeneChip Human Transcriptome Array 2.0 (Affimetrix) at baseline and at the end of the body weight loss period (16 Weeks)

mRNA expression will be measured by GeneChip Human Transcriptome Array 2.0 (Affimetrix) at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

microARNs levels in exosomes will be measured by NGS Illumina Myseq at baseline and at the end of the body weight loss period (16 Weeks)

microARNs levels in exosomes will be measured by next-generation sequencing (NGS) Illumina Myseq at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

DNA oxidation will be measured by 8-hydroxy-deoxyguanosine at baseline and at the end of the body weight loss period (16 Weeks)

DNA oxidation will be measured by 8-hydroxy-deoxyguanosine at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Serum glucose levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Serum glucose levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Serum insulin concentration will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Serum insulin concentration will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Serum free fatty acids, triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol concentrations will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Serum free fatty acids, triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol concentrations will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Serum total protein concentration will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Serum total protein concentration will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Serum uric acid levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Serum uric acid levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Serum transaminases (AST & ALT) concentrations will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Serum transaminases (AST & ALT) concentrations will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Serum homocystein concentration will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Serum homocystein concentration will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

VEGF levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

VEGF levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

ADMA levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

ADMA levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

PAI-1 concentration will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

PAI-1 concentration will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Nitric oxide levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Nitric oxide levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Changes in diastolic and systolic blood pressure will be measured at baseline and at the end of the body weight loss period (16 Weeks)

Changes in diastolic and systolic blood pressure will be measured at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

C-Reactive Protein levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

C-Reactive Protein levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

IL-6 and IL-10 levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

IL-6 and IL-10 levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

TNF-alpha levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

TNF-alpha levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Adiponectin levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Adiponectin levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Chemerin levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Chemerin levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Leptin levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Leptin levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Apelin levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Apelin levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Haptoglobin levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Haptoglobin levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Amyloid A levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Amyloid A levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Leukocytes levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Leukocytes levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Levels of LDL-ox in plasma will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Levels of LDL-ox in plasma will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Glutathione peroxidase activity will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Glutathione peroxidase activity will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Reduced and oxidized glutathione levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Reduced and oxidized glutathione levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Superoxide dismutase levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Superoxide dismutase levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Serum isoprostanes levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Serum isoprostanes levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

MDA concentration will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

MDA concentration will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Plasma monoamines (dopamine, dopac, homovalic acid, serotonin, noradrenalin) levels will be measured in a fasting state at baseline and at the end of the body weight loss period (16 Weeks)

Plasma monoamines (dopamine, dopac, homovalic acid, serotonin, noradrenalin) levels will be measured in a fasting state at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Physical activity level will be measured by a validated physical activity questionnaire and by a pedometer at baseline and at the end of the body weight loss period (16 Weeks)

Physical activity level will be measured by a validated physical activity questionnaire and by a pedometer at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Depression degree will be measured by the Beck Depression Inventory at baseline and at the end of the body weight loss period (16 Weeks)

Depression degree will be measured by the Beck Depression Inventory at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Anxiety degree will be measured by the State-Trait Anxiety Inventory (STAI) at baseline and at the end of the body weight loss period (16 Weeks)

Anxiety degree will be measured by the State-Trait Anxiety Inventory (STAI) at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Chronotype will be defined by two questionnaires at baseline and at the end of the intervention period (16 Weeks)

Chronotype will be defined by two questionnaires at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Food intake will be evaluated by a 72 hours dietary record at baseline and at the end of the body weight loss period (16 Weeks)

Food intake will be evaluated by a 72 hours dietary record and by a validated Food Frequency Questionnaire at baseline and at the end of the body weight maintenance period (40 Weeks)

Satiety will be evaluated by the Visual Analogue Scale (VAS) at baseline and at the end of the body weight loss period (16 Weeks)

Satiety will be evaluated by the Visual Analogue Scale (VAS) at the end of the body weight loss period (16 Weeks) and at the end of the body weight maintenance period (40 Weeks)

Inclusion Criteria: Body Mass Index (BMI) between 25 and 40 kg/m2 Physical examination and vital signs normal, or is considered abnormal, but clinically insignificant by researcher. In the case of individuals with chronic stable dose drug treatment and during the last 3 previous months at baseline, the investigator will assess their possible inclusion. Exclusion Criteria: BMI less than 25 or higher than 40 kg/m2 Pregnant women Breastfeeding period. If artificial feeding until 6 months after birth. Type 1 diabetes Severe kidney diseases Severe digestive system diseases Electrolyte disorders (disorders of sodium, potassium, calcium, chlorine, phosphorus, magnesium) Acute cardiovascular diseases Cancer Anemia Eating disorders Recent prescription drug treatment (without stable doses scheduled) Drug therapy that can influence weight loss as corticosteroids. Some type of cognitive impairment and / psychic Subjects in which poor collaboration or, in the investigator's opinion, have difficulty following the procedures of the study is foreseen Lack of commitment (at the discretion of the investigator) with the intervention, suspected non-compliance, or real difficulties to follow the development of the study.

Centre for Nutrition Research, University of Navarra. CIBER Obesity and Physiopathology of Nutrition (CIBERobn), Institute of Health Carlos III Madrid Spain

Centre for Nutrition Research, University of Navarra. CIBER Obesity and Physiopathology of Nutrition (CIBERobn), Institute of Health Carlos III Madrid Spain

Centre for Nutrition Research, University of Navarra. CIBER Obesity and Physiopathology of Nutrition (CIBERobn), Institute of Health Carlos III Madrid Spain

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