Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation...

Area of Science:

• Metabolic Health
• Exercise Physiology
• Obesity Research

Background:

• Weight loss is crucial for obesity treatment and type 2 diabetes (T2D) prevention.
• Clinical implementation is hindered by perceived burden and varied responses.
• Personalized interventions are needed to improve success rates.

Purpose of the Study:

• To identify predictive factors for successful weight loss in women with obesity following sequential exercise.
• To explore whole body and gut metabolic flexibility (MetFlex) as predictors of weight loss outcomes.

Main Methods:

• A 2-stage approach: predictive validation study and a randomized cross-over controlled trial.
• Participants: Women aged 25-45 with obesity (BMI > 30).
• Intervention: Progressive aerobic exercise (treadmill, bicycle ergometer). Measurements include fat mass, fat-free mass, MetFlex (ΔRQ), insulin sensitivity, glucose tolerance, HbA1c, microbiome, and metabolomic signatures.

Main Results:

• Recruitment began January 2024; 12 participants enrolled and randomized.
• Preliminary data expected by 2026.
• Ongoing recruitment and intervention phases.

Conclusions:

• This study will explore metabolic flexibility as an ex ante predictor of successful weight loss.
• Provides proof of concept for personalized lifestyle interventions.
• Aims to enhance the effectiveness of exercise interventions for weight management.