Obesity
Conditions
Keywords
Brain, Genes, Environment, Etiology, Reward, Satiety Response, Central Nervous System, Magnetic Resonance Imaging, Twins, Monozygotic, Overweight, Obesity
Brief summary
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.
Interventions
None listed
Sponsors
Amsterdam UMC, location VUmc
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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 lean and obese subjects with either high or low genetic obesity risk. | Baseline (one measurement) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding basal metabolic rate | Baseline (one measurement) | 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. |
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding fasting circulating biomarker levels | Baseline (one measurement) | 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. |
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding autonomic nervous system balance | Baseline (one measurement) | 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. |
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding dietary intake | Baseline (one measurement) | 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. |
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding physical activity level | Baseline (one measurement) | Physical activity level will be measured as metabolic equivalent of task (METs)-hours per week using seven-day ActiGraph triaxial accelerometry at home. |
| The difference between individuals at high versus those at low genetic obesity risk regarding physical activity level | Baseline (one measurement) | Physical activity level will be measured as metabolic equivalent of task (METs)-hours per week using seven-day ActiGraph triaxial accelerometry at home. |
| The difference between individuals at high versus those at low genetic obesity risk regarding basal metabolic rate | Baseline (one measurement) | 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. |
| The difference between individuals at high versus those at low genetic obesity risk regarding fasting circulating biomarker levels | Baseline (one measurement) | 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. |
| The difference between individuals at high versus those at low genetic obesity risk regarding autonomic nervous system balance | Baseline (one measurement) | 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. |
| The difference between individuals at high versus those at low genetic obesity risk regarding dietary intake | Baseline (one measurement) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding gut microbiota composition | Baseline (one measurement) | Gut microbiota composition (ratio between various gut microbiota species) will be assessed by identifying microbial phylotypes in a feces sample using 16S ribosomal RNA molecule-based approaches of diagnostic analysis. Function of gut microbiota will be investigated using metaproteomics analysis techniques that include mass-spectroscopy methodologies. Please note: this outcome measure is conditional to available budget. |
| The difference between individuals at high versus those at low genetic obesity risk regarding gut microbiota composition | Baseline (one measurement) | Gut microbiota composition (ratio between various gut microbiota species) will be assessed by identifying microbial phylotypes in a feces sample using 16S ribosomal RNA molecule-based approaches of diagnostic analysis. Function of gut microbiota will be investigated using metaproteomics analysis techniques that include mass-spectroscopy methodologies. Please note: this outcome measure is conditional to available budget. |
| The difference within obesity-discordant monozygotic (MZ) twin pairs regarding epigenetic changes | Baseline (one measurement) | Epigenetic changes will be assessed by measuring global DNA methylation (%) and locus specific DNA methylation (%) in regions of selected loci using a mass spectrometry-based method. Loci will be selected on the basis of their previously shown features of epigenetic regulation and their involvement in cardiovascular and metabolic disease. Please note: this outcome measure is conditional to available budget. |
| The difference between individuals at high versus those at low genetic obesity risk regarding epigenetic changes | Baseline (one measurement) | Epigenetic changes will be assessed by measuring global DNA methylation (%) and locus specific DNA methylation (%) in regions of selected loci using a mass spectrometry-based method. Loci will be selected on the basis of their previously shown features of epigenetic regulation and their involvement in cardiovascular and metabolic disease. Please note: this outcome measure is conditional to available budget. |
Countries
Netherlands
Outcome results
None listed