Neural Mechanisms for Appetitive Responses to High Reward Foods

Study Overview
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Brief Summary
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This study is aimed at understanding neuroendocrine responses to different types of sugars and how this influences feeding behavior among lean, overweight, and obese individuals.

Detailed Description
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The investigators have previously combined functional magnetic resonance imaging (fMRI) with hormonal and behavioral assessments to better understand the impacts of glucose and fructose on appetite and its central regulation in humans and have made important observations in lean individuals linking fructose consumption to overeating and obesity. The investigators now propose to expand this work by examining the impacts of glucose and fructose ingested together (sucrose), as occurs in real life, and by examining effects of a common non-nutritive sweetener, sucralose, on brain and appetitive response. The investigators propose a random-order crossover design to determine the effects of caloric and non-nutritive sweeteners among lean, overweight, and obese participants. The investigators will measure circulating levels of hormones involved in satiety signaling, quantify food intake, and measure brain activity using blood-oxygen level dependent and arterial spin labeling methods and functional connectivity analyses.

Official Title
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Neural Mechanisms for Appetitive Responses to High Reward Foods

Conditions
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Appetitive Behavior, Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-35 years, right-handed, weight change <2% for at least 3 months prior to participation, no history of diabetes or other significant medical problems, fasting glucose <126 mg/dl. Lean group: BMI of 19-24.9 kg/m2 Obese Group: BMI 30-40 kg/m2 Overweight Group: BMI of 25-29.9 kg/m2 Exclusion Criteria: Neurological, psychiatric or addiction disorder, fasting glucose ≥126 mg/dl, use of prescription medication (with the exception of contraceptives), tobacco use, contraindications to MRI scanning (detailed in Protection of Human Subjects), fructose intolerance, history of eating disorder, actively trying to lose weight.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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 |
| --- | --- |
| obese<br>Individuals ages 18 to 35 years of age with body mass index (BMI) 30-40 kg/m2 | |
| lean<br>Individuals ages 18 to 35 years of age with BMI of 19-24.9 kg/m2 | |
| overweight<br>Individuals ages 18 to 35 years of age with BMI of 25-29.9 kg/m2 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Blood oxygen level-dependent (BOLD) signal responses to food vs non-food cues after ingestion of different types of sugar. BOLD signal responses to food cues will be compared at the level of whole brain and within a priori regions of interest. | These will be compared between ingestion of drinks and at level of whole brain and in regions of interest | Sessions 1, 2, 3, 4 | 
| Cerebral Blood Flow Response | Arterial spin labeling with be used to determine brain areas with relative increases or decreases in CBF after ingestion of sucrose, glucose, or sucralose. | Sessions 1, 2, 3, 4 | 
| Systemic Metabolite and Hormone Responses | The effects of sugar ingestion on changes in systemic metabolite (glucose) and hormone (insulin, GLP-1, leptin, ghrelin, peptide YY) levels will be assessed. | Sessions 1, 2, 3, 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Connectivity between regions involved in regulation of food intake | Investigators will perform a physiological-psychological-interaction (PPI) analysis using the nucleus accumbens as the seed to explore brain regions showing increased functional connectivity to the seed during the food-cue task. | Sessions 1, 2, 3, 4 | 
| Appetite Ratings | Ratings of hunger and desire for food in response to food vs non-food cues will be analyzed using a repeated-measures ANOVA with condition (glucose, sucrose, sucralose) and stimulus (food vs non-food) as within-subject factors. | Sessions 1, 2, 3, 4 | 
| Ad Libitum Food Intake | Total calories consumed and percent calories from sugar, fat and protein will be compared between conditions. | Sessions 1, 2, 3, 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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functional magnetic resonance imaging, eating behavior, sugar