KFO 218/1: Hormonal regulation of body weight maintenance

Obesity is one of the most prevalent disorders that challenge the health care systems worldwide due to the enormous implications for morbidity, mortality and quality of life of obese individuals. Various strategies, including lifestyle but also pharmacological approaches, have been shown to support or induce weight loss on the short run. However, those strategies usually fail to establish a sustained energy balance at a novel setpoint and do not stabilize body weight on the long term. In contrast, many individuals regain weight relatively fast and often the post-intervention body weight even increases compared to baseline (weight cycling), a phenomenon which may be associated with a worse outcome in terms of complications than adiposity itself.
Loss of body weight in obese individuals is associated with a paradox counterregulation that reduces energy expenditure. Recent studies demonstrated that hormonal mechanisms contribute significantly to this phenomenon. A coordinated hormonal response favours weight regain and is therefore of major importance for the long term maintenance of body weight. The opportunity to modify these endocrine components of weight regain implies therapeutic interventions to improve the success of body weight maintenance. A more detailed and individualised investigation of these counter-regulatory endocrine responses under weight loss are required to translate these findings into hormone-based clinical treatment trials for weight loss maintenance. Therefore the strategic objective of this Clinical Research Group (CRG) is to identify and characterise hormonal mechanisms counterbalancing weight maintenance after a previous period of negative energy balance.
A central randomized controlled trial investigating mechanisms of weight maintenance in children, adolescents and adults will be surrounded by various clinical and experimental projects targeting specific aspects of hormonal counter-regulation after weight loss. Detailed phenotyping including biopsies will be performed and systemic and local metabolism will be investigated by applying specific but also profiling technologies. Finally, the clinical trial will include children and adults, which will allow the identification of distinct hormonal counter-regulating mechanisms in those different age groups. Participating basic science projects analyse various potentially novel aspects of energy homeostasis. The interaction of those basic science projects and the direct link to the central human trial is supported by standard operating procedures in the characterisation of hormonal systems in all investigated animal models.
The proposed structure of the CRG takes advantage of the expertise in clinical and basic research within the topics of endocrinology and energy homeostasis in the region of Berlin/Potsdam and facilitates the translation of experimental findings to therapeutic approaches resulting in improved weight maintenance and metabolic health.