Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Central Reward System
- Conditions
- Insulin ResistanceObesity, Morbid
- Interventions
- Procedure: Bariatric surgery
- Registration Number
- NCT05080205
- Lead Sponsor
- Turku University Hospital
- Brief Summary
Background: Morbid obesity is associated with decreased brain µ-opioid receptor availability, possibly resulting in higher food intake needed to gain pleasure from eating. This decrease seems to normalize already 6 months after bariatric surgery, but the longer-term effects have not been studied. Obesity and insulin resistance result in significantly increased brain insulin-stimulated glucose uptake, whereas in every other tissue glucose uptake is lower. One possible explanation to this could be central inflammation and activation of brain glial cells, which has been shown to occur in animal models of obesity. Obesity has also been shown to associate with increased risk of Alzheimer's disease and cognitive decline in several studies.
Aims: The first objective of this study is to both study the effects of bariatric surgery as well as compare the effects of gastric bypass and sleeve gastrectomy on food-associated pleasure, extending the follow-up period to 2 years postoperatively. The second aim is to investigate the effect of morbid obesity and weight loss on brain inflammation and gliosis and its association with increased brain insulin-stimulated glucose uptake. Furthermore, association of obesity, insulin resistance, central inflammation and neurocognitive dysfunction are evaluated.
- Detailed Description
Methods: A total of 60 morbidly obese subjects, 30 assigned for Roux-en-Y gastric bypass and 30 for sleeve gastrectomy according to routine treatment protocols will be recruited for this study. A control group of 30 healthy subjects will also be recruited. We will perform 1) structural MRI and MRS, 2) functional MRI during tasting and visual food cues, 3) PET imaging of µ-opioid receptor availability using \[11C\]-carfentanil, 4) PET imaging of cerebral inflammation and astrocyte activation using \[11C\]-PK11195, 5) measurement of whole-body and tissue insulin sensitivity by combining hyperinsulinemic, euglycemic clamp with \[18F\]-FDG-PET, 6) neuropsychological testing. The control group will only be studied once, whereas study procedures will be repeated for the morbidly obese before very-low calorie diet and 6, 12 and 24 months postoperatively.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Morbidly obese subjects Bariatric surgery Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy)
- Primary Outcome Measures
Name Time Method Change in central inflammation Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively Assessment of brain glial cell activation using \[11C\]-PK11195 tracer and positron emission tomography
- Secondary Outcome Measures
Name Time Method Changes in brain μ-opioid receptor availability using PET imaging Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively Assessment of brain μ-opioid receptor availability using \[11C\]-carfentanil tracer and positron emission tomography
Changes in cognitive function studied with testing Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively Neuropsychological testing focusing on memory, decision-making and inhibition
Changes in central reward system using fMRI imaging Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively Assessment of brain reward system activation after visual/taste cues using functional MRI
Changes in whole-body insulin sensitivity usign FDG-PET imaging Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively Assessment of whole-body insulin sensitivity using hyperinsulinemic, euglycemic clamp
Changes in tissue-specific insulin sensitivity using FDG-PET imaging Controls: 0 months; Morbidly obese: preoperatively Assessment of insulin-stimulated glucose uptake in the brain, liver, skeletal muscle and adipose tissue by performing positron emission tomography with \[18F\]-fluorodeoxyglucose tracer during hyperinsulinemic, euglycemic clamp
Trial Locations
- Locations (1)
Turku PET Centre
🇫🇮Turku, Finland