Study Design
Two-Study Translational Approach: Human Clinical + Mouse Mechanistic
To test the hypothesis that baseline diet-induced thermogenesis (DIT) predicts 12-month weight loss in patients treated with GLP-1 receptor agonists
120
Patients
3
Centers
Validate DIT-weight loss relationship in genetically defined mouse models and explore mechanistic pathways through BAT, WAT, and muscle tissue analysis
~200 mice across 4 experiments
Mice
2
Centers
Human Study
PRIMARY: LPMT → DIT
Secondary: High-Fat → MetFlex
Secondary: ECS profiling
PREDICTION MODEL
Mouse Study
Mouse LPMT simulation
Indirect calorimetry
Tissue ECS analysis
MECHANISTIC INSIGHT
Correlation between baseline DIT (from LPMT) and % total body weight loss at 12 months
Baseline DIT (from LPMT) → % Total Body Weight Loss at 12 months
Metabolic Flexibility
High-fat meal challenge → RQ shift, fat oxidation as predictor of weight loss
Endocannabinoid System
Baseline ECS markers (AEA, 2-AG, PEA, OEA) as predictors of weight loss
Body Composition (MRI)
AMRA Medical MRI for VAT, ASAT, liver fat, muscle volume changes
Muscle Function
Grip strength and chair stand test to monitor lean mass preservation
Mouse Mechanistic Insights
Tissue analyses (BAT, WAT, muscle) to explain DIT-weight loss relationship
18-Month Follow-up
Phone call for long-term weight maintenance assessment
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