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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| obese | Individuals ages 18 to 35 years of age with body mass index (BMI) 30-40 kg/m2 | ||
| lean | Individuals ages 18 to 35 years of age with BMI of 19-24.9 kg/m2 | ||
| overweight | Individuals ages 18 to 35 years of age with BMI of 25-29.9 kg/m2 |
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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Participants in the greater Los Angeles area will be recruited. Lean, overweight, and obese participants will be recruited.
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| Name | Affiliation | Role |
|---|---|---|
| Kathleen Page, MD | University of Southern California | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alexandra Yunker | Los Angeles | California | 90089 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40140714 | Derived | Chakravartti SP, Jann K, Veit R, Liu H, Yunker AG, Angelo B, Monterosso JR, Xiang AH, Kullmann S, Page KA. Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights. Nat Metab. 2025 Mar;7(3):574-585. doi: 10.1038/s42255-025-01227-8. Epub 2025 Mar 26. | |
| 38427387 | Derived |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | May 11, 2022 | |
| Reset | Feb 9, 2023 | |
| Release | Jun 13, 2024 | |
| Unrelease | Jun 14, 2024 | |
| Release | Jun 14, 2024 | |
| Unrelease | Jun 19, 2024 | |
| Release | Jun 20, 2024 | |
| Unrelease | Jul 1, 2024 | |
| Release | Jul 1, 2024 | |
| Unrelease | Jul 18, 2024 | |
| Release | Jul 18, 2024 | |
| Reset | Oct 11, 2024 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| May 11, 2022 | Feb 9, 2023 | |||
| Jun 13, 2024 | Jun 14, 2024 |
| ID | Term |
|---|---|
| D001070 | Appetitive Behavior |
| D009765 | Obesity |
| D005247 | Feeding Behavior |
| ID | Term |
|---|---|
| D001522 | Behavior, Animal |
| D001519 | Behavior |
| D050177 | Overweight |
| D044343 | Overnutrition |
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Blood Samples
| 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 |
| Smith A, Page KA, Smith KE. Associations between affect dynamics and eating regulation in daily life: a preliminary ecological momentary assessment study. Cogn Emot. 2024 Aug;38(5):818-824. doi: 10.1080/02699931.2024.2323478. Epub 2024 Mar 1. |
| 35491674 | Derived | Alves JM, Yunker AG, Luo S, Jann K, Angelo B, DeFendis A, Pickering TA, Smith A, Monterosso JR, Page KA. FGF21 response to sucrose is associated with BMI and dorsal striatal signaling in humans. Obesity (Silver Spring). 2022 Jun;30(6):1239-1247. doi: 10.1002/oby.23432. Epub 2022 May 2. |
| 34581796 | Derived | Yunker AG, Alves JM, Luo S, Angelo B, DeFendis A, Pickering TA, Monterosso JR, Page KA. Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing: A Randomized Crossover Trial. JAMA Netw Open. 2021 Sep 1;4(9):e2126313. doi: 10.1001/jamanetworkopen.2021.26313. |
| 33300990 | Derived | Yunker AG, Luo S, Jones S, Dorton HM, Alves JM, Angelo B, DeFendis A, Pickering TA, Monterosso JR, Page KA. Appetite-Regulating Hormones Are Reduced After Oral Sucrose vs Glucose: Influence of Obesity, Insulin Resistance, and Sex. J Clin Endocrinol Metab. 2021 Mar 8;106(3):654-664. doi: 10.1210/clinem/dgaa865. |
| Jun 14, 2024 | Jun 19, 2024 |
| Jun 20, 2024 | Jul 1, 2024 |
| Jul 1, 2024 | Jul 18, 2024 |
| Jul 18, 2024 | Oct 11, 2024 |
| D009748 |
| Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |