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Aim 1: To measure levels of microglia using the radiotracer [11C]PBR28 and PET brain imaging in obese (n=50) vs. lean individuals (n=50). The investigators will recruit 100 subjects who will participate in a single [11C]PBR28 scan to measure levels of TSPO, a marker of microglia.
Aim 2: To determine differences in brain functional connectivity at rest and in response to a decision- making task in obese (n=50) vs. lean individuals (n=50) using fMRI imaging. The same subjects from Aim 1 will participate in a resting state functional magnetic resonance imaging (fMRI) followed by a decision making task during fMRI acquisition.
Aim 3: To assess whether acute elevation of lipid levels through intralipid infusion in lean, healthy individuals (n=20) will induce microglial activation. 20 lean individuals will be recruited to participate in a paradigm that includes a baseline [11C]PBR28 scan, an infusion of intralipid, and a second [11C]PBR28 scan approximately 4 hours post intralipid infusion. The investigators will attempt to utilize subjects from aim 1 in order to use their baseline scans for this paradigm.
Aim 4: To determine whether there are differences in levels of microglia between individuals with and without type 1 diabetes (n=20). 20 patients with diabetes (type 1 diabetes or type 2 diabetes)will be recruited to participate in a single [11C]PBR28 scan to compare to Aim 1 participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Baseline [11C]PBR28 PET Scan | No Intervention | Subjects will complete a 120-minute baseline [11C]PBR28 PET scan. | |
| Post-Intralipid Infusion [11C]PBR28 PET Scan | Experimental | Subjects will complete a second 120-minute [11C]PBR28 PET scan 4 hours after Intralipid Infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intralipid Infusion | Drug | Intralipid 20% (a 20% IV fat emulsion) is a sterile, non-pyrogenic fat emulsion prepared for IV administration as a source of calories and essential fatty acids. It is made up of 20% soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin and water for injection. In addition, sodium hydroxide has been added to adjust the pH so that the final product pH is 8. |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline [11C]PBR28 VT values | [11C]PBR28 VT values in our primary regions of interest (PFC and hippocampus) from PET Scan. Linear mixed-effect models will be conducted to evaluate differences in [11C]PBR28 VT values between lean, healthy controls (n=40) and individuals with obesity (n=40), controlling for rs6971 genotype, age, and sex. | At baseline |
| Post-Intralipid [11C]PBR28 VT values | [11C]PBR28 VT values in our primary regions of interest (PFC and hippocampus) from PET Scan. Linear mixed-effect models will be conducted to evaluate differences in [11C]PBR28 VT values between lean, healthy controls (n=40) and individuals with obesity (n=40), controlling for rs6971 genotype, age, and sex. | Approximately 3 Hours After Intralipid Infusion |
| Baseline Functional Connectivity | ICD values will be obtained from primary a priori regions of interest (vmPFC and hippocampus) with PET Scan. Independent t-tests will be used to compare the ICD data between the study groups. | At baseline |
| Post-Intralipid Functional Connectivity | ICD values will be obtained from primary a priori regions of interest (vmPFC and hippocampus) with PET Scan. Independent t-tests will be used to compare the ICD data between the study groups. | Approximately 3 Hours After Intralipid Infusion |
| Baseline Microglial Activation | Regional [11C]PBR28 VT values from pre-lipid infusion PET Scan | At baseline |
| Post-Intralipid Microglial Activation | Percent change in regional [11C]PBR28 VT values from pre-lipid infusion PET Scan to post-lipid infusion PET Scan will be calculated across brain regions. Increased microglial activation will be measured as a 20% or more increase in TSPO levels from scan 1 to scan 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline Visual Attention | Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). | At baseline |
| Post-Intralipid Infusion Visual Attention | Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). |
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Inclusion Criteria:
Exclusion Criteria:
Note: If a subject tests positive for an illicit substance, the PI will determine if the substance would interfere with the results and may terminate participation if applicable. Results of the test would only be noted in the subjects de-identified chart to document the occurrence.
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| Name | Affiliation | Role |
|---|---|---|
| Kelly Cosgrove, PhD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University | New Haven | Connecticut | 06519 | United States |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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|
| Approximately 3 Hours After Intralipid Infusion |
| Approximately 1 Hour After Intralipid Infusion |
| Baseline Visual Learning | Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). | At baseline |
| Post-Intralipid Infusion Visual Learning | Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). | Approximately 1 Hour After Intralipid Infusion |
| Baseline Verbal Memory | Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall). | At baseline |
| Post-Intralipid Verbal Memory | Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall). | Approximately 1 Hour After Intralipid Infusion |
| Baseline Executive Function | Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). | At baseline |
| Post-Intralipid Executive Function | Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). | Approximately 1 Hour After Intralipid Infusion |
| Baseline Visual-Motor Processing Speed | Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). | At baseline |
| Post-Intralipid Visual-Motor Processing Speed | Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). | Approximately 1 Hour After Intralipid Infusion |
| Baseline Working Memory | Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory). | At baseline |
| Post-Intralipid Working Memory | Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory). | Approximately 1 Hour After Intralipid Infusion |
| Baseline Social Cognition | Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition). | At baseline |
| Post-Intralipid Social Cognition | Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition). | Approximately 1 Hour After Intralipid Infusion |
| Baseline Reward Responsiveness | Reward responsiveness will be quantified via computerized Probabilistic Reward Task | At baseline |
| Post-Intralipid Reward Responsiveness | Reward responsiveness will be quantified via computerized Probabilistic Reward Task | Approximately 1 Hour After Intralipid Infusion |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |