Obesity and Brain: Genes and Environment

Study Overview
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Brief Summary
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The aim of this study is to investigate the effects of genetic and environmental risk factors on central nervous system (CNS) reward and satiety circuits in the etiology of obesity. The investigators will also investigate to what extent the alterations in CNS reward and satiety circuits are a cause or a consequence of the development of obesity.

Official Title
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The Role of Central Reward and Satiety Centers in the Etiology of Obesity: Genetic and Environmental Influences

Conditions
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Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Male or female Stable bodyweight (<5% reported weight change during previous 3 months) Women: regular menstruation cycle (to exclude possible menstruation cycle effects) Normal fasting blood glucose Exclusion Criteria: Left handedness Known diabetes or abnormal fasting blood glucose Serious heart, pulmonary, hepatic or renal disease, malignant or hematological disease Metabolic disorders (uncontrolled adrenal/thyroid disease) Women: irregular menstruation cycle Neurological or psychiatric illness Pregnancy or breast feeding Alcohol abuse Nicotine abuse Claustrophobia or metal implants Visual disability Participation in another study Inability to understand the protocol or to give informed consent Current/chronic use of following medication: antihyperglycemic agents, glucocorticoids, centrally acting drugs, cytostatics, immune suppressants, potentially addictive medications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Monozygotic twin pairs<br>15 monozygotic twin pairs discordant for obesity | |
| Genetic predisposition for obesity<br>15 obese and 15 non-obese individuals with a high genotype obesity risk score and 15 obese and 15 non-obese individuals with a low genotype obesity risk score. Genotype obesity risk score will be based on genome wide association single-nucleotide polymorphisms (SNP's) associated with obesity. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in neuronal activity in CNS reward and satiety circuits as represented by BOLD functional magnetic resonance imaging (fMRI) signal change from baseline (%) in response to food-related stimuli within obesity discordant MZ twin pairs. |  | Baseline (one measurement) | 
| The difference in neuronal activity in CNS reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) in response to food-related stimuli between individuals at high verses low genetic obesity risk. |  | Baseline (one measurement) | 
| The difference in neuronal activity in CNS reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) in response to food-related stimuli between lean and obese subjects with either high or low genetic obesity risk. |  | Baseline (one measurement) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding dietary intake | Dietary intake will be measured as quantitative (kcal/day) and qualitative (energy density (kcal/kg) and macronutrient composition (%)) dietary intake using A) a choice lunch buffet on the visit day and B) the 24 hours recall method on two week days and one weekend day at home. | Baseline (one measurement) | 
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding physical activity level | Physical activity level will be measured as metabolic equivalent of task (METs)-hours per week using seven-day ActiGraph triaxial accelerometry at home. | Baseline (one measurement) | 
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding basal metabolic rate | Basal metabolic rate will be measured in kcal/day using oxygen consumption and carbon dioxide production measured by indirect calorimetry using a ventilated hood system. | Baseline (one measurement) | 
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding fasting circulating biomarker levels | Fasting circulating biomarker levels (glucose (mmol/l), HbA1c (mmol/mol), insulin (pmol/l), C-peptide (nmol/l), glucagon (pmol/l), triglycerides (mmol/l), HDL-cholesterol (mmol/l) and LDL-cholesterol (mmol/l)) will be measured in a fasting blood sample. | Baseline (one measurement) | 
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding autonomic nervous system balance | Autonomic nervous system balance will be assessment based on measurements of A) heart rate variability (HRV; calculated as root mean square of successive R-R interval differences (RMSSD) in ms2); B) respiratory rate (RR; breaths/min) and C) respiratory sinus arrhythmia (RSA; ms) in resting conditions and in response to a mental arithmetic task using an electro- and impedance cardiogram. | Baseline (one measurement) | 
| The difference between individuals at high versus those at low genetic obesity risk regarding dietary intake | Dietary intake will be measured as quantitative (kcal/day) and qualitative (energy density (kcal/kg) and macronutrient composition (%)) dietary intake using A) a choice lunch buffet on the visit day and B) the 24 hours recall method on two week days and one weekend day at home. | Baseline (one measurement) | 
| The difference between individuals at high versus those at low genetic obesity risk regarding physical activity level | Physical activity level will be measured as metabolic equivalent of task (METs)-hours per week using seven-day ActiGraph triaxial accelerometry at home. | Baseline (one measurement) | 
| The difference between individuals at high versus those at low genetic obesity risk regarding basal metabolic rate | Basal metabolic rate will be measured in kcal/day using oxygen consumption and carbon dioxide production measured by indirect calorimetry using a ventilated hood system. | Baseline (one measurement) | 
| The difference between individuals at high versus those at low genetic obesity risk regarding fasting circulating biomarker levels | Fasting circulating biomarker levels (glucose (mmol/l), HbA1c (mmol/mol), insulin (pmol/l), C-peptide (nmol/l), glucagon (pmol/l), triglycerides (mmol/l), HDL-cholesterol (mmol/l) and LDL-cholesterol (mmol/l)) will be measured in a fasting blood sample. | Baseline (one measurement) | 
| The difference between individuals at high versus those at low genetic obesity risk regarding autonomic nervous system balance | Autonomic nervous system balance will be assessment based on measurements of A) heart rate variability (HRV; calculated as root mean square of successive R-R interval differences (RMSSD) in ms2); B) respiratory rate (RR; breaths/min) and C) respiratory sinus arrhythmia (RSA; ms) in resting conditions and in response to a mental arithmetic task using an electro- and impedance cardiogram. | Baseline (one measurement) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain, Genes, Environment, Etiology, Reward, Satiety Response, Central Nervous System, Magnetic Resonance Imaging, Twins, Monozygotic, Overweight, Obesity