Urinary Signatures Predict Calorie Restriction-Mediated Weight Loss in Obese Diversity Outbred Mice

Area of Science:

• Metabolomics
• Obesity Research
• Personalized Nutrition

Background:

• Predictive analytics using metabolomic profiles are crucial for personalizing dietary interventions.
• Obesity is a complex condition with diverse responses to weight loss strategies.
• Identifying biomarkers for calorie restriction (CR) responsiveness is essential for effective weight management.

Purpose of the Study:

• To identify urinary metabolite signatures that predict responsiveness to calorie restriction (CR) in a mouse model of obesity.
• To investigate sex-specific differences in metabolite profiles related to CR success.
• To develop predictive models for CR-mediated weight loss.

Main Methods:

• Obese Diversity Outbred (DO) mice were subjected to a high-fat diet followed by an 8-week calorie restriction regimen.
• Urinary metabolomics was performed using targeted, semi-quantitative analysis.
• Mice were categorized into CR responders and nonresponders based on body weight change; multivariate analyses were used for prediction modeling.

Main Results:

• Elevated urinary glutamic acid and hydroxyproline distinguished CR responders from nonresponders, irrespective of sex.
• Sex-specific metabolite signatures were identified: glutamic acid, hydroxyproline, and putrescine in males; glutamic acid, hydroxyproline, dopamine, histamine, lysine, and spermine in females.
• Multivariate models demonstrated moderate to robust prediction of CR-mediated weight loss, particularly in females and combined sexes.

Conclusions:

• Urinary metabolomic profiles, specifically glutamic acid and hydroxyproline, serve as reliable predictors of weight loss success following calorie restriction.
• Metabolic pathways such as arginine and proline metabolism are implicated in the adaptive response to CR.
• These findings support the potential for metabolomics-driven personalization of dietary interventions for obesity.