Establishing a specific metabolic phenotyping technique to personalize obesity therapy in morbidly obese individuals

• Applicant: Dr. Tim Hollstein
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 508000993

One challenge in obesity research is to identify individuals prone to weight gain and resistant to weight loss. According to recent studies, such individuals can be identified by measuring the metabolic response to acute fasting as they decrease their energy expenditure to a greater extend during fasting which reveals an underlying “thrifty” metabolic phenotype. In controlled interventional studies, thrifty individuals lost less weight during a hypocaloric diet while they gained more weight during overfeeding compared to individuals with a more “spendthrift” phenotype.Until now, metabolic phenotyping is achieved by measuring the 24h energy expenditure response to 24h fasting in a whole-room indirect calorimeter. However, this procedure is complex and rarely available. Therefore, metabolic phenotyping did not yet arrive in clinical practice. Furthermore, there is no known biomarker of the thrifty metabolic phenotype. The main objective of this present work is therefore to establish a specific metabolic phenotyping technique for the identification of thrifty individuals which can also be applied in clinical routine. Previous studies suggest that the metabolic phenotype may be identified by the measurement of resting metabolic rate before and after fasting.In this study, resting metabolic rate will be measured before and after 24 hours of fasting in individuals with morbid obesity (BMI > 40 kg/m2) who will undergo a 12-week very-low-calorie-diet (800 kcal/day) as part of a multimodal obesity therapy. The hypothesis: Thrifty individuals, who decrease their resting metabolic rate during fasting, will be more resistant to weight loss compared to spendthrift individuals, who increase their resting metabolic rate during fasting. Additionally, blood, urine and saliva samples will be analyzed before and after fasting with two established metabolomics techniques and related to the change in resting metabolic rate to identify a biomarker or a biomarker pattern for the thrifty phenotype.Looking ahead, a simplified measurement of the metabolic phenotype may lead to a personalized obesity therapy, such that pharmacological or surgical weight loss therapies or alternative ways to weight reduction may be preferentially offered to morbidly obese individuals with a thrifty phenotype, who poorly respond to traditional weight loss interventions.

• DFG Programme: Research Grants