Study Design

Two-Study Translational Approach: Human Clinical + Mouse Mechanistic

Clinical Human Study
Prospective, multicenter observational cohort

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

DEESNL
Mechanistic Mouse Study
Interventional preclinical study

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

BEFR
Translational Framework
Parallel human-mouse approach for prediction and mechanism

Human Study

PRIMARY: LPMT → DIT

Secondary: High-Fat → MetFlex

Secondary: ECS profiling

PREDICTION MODEL

Translation

Mouse Study

Mouse LPMT simulation

Indirect calorimetry

Tissue ECS analysis

MECHANISTIC INSIGHT

Primary Endpoint

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

Secondary Endpoints (Exploratory)

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

Discussion: Study Design

Sign in to join the discussion

Sign in
T
Tim Hollstein12/15/2025

This is a test comment!