KFO 218:  Hormonal Regulation of Body Weight Maintenance

• Subject Area: Medicine
• Term: from 2009 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 101434729

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 stabilise 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. This coordinated hormonal response favours weight regain and is, therefore, of major importance for the long-term maintenance of body weight. The opportunity to modify 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. Further endocrine responses like sex steroids, glucocorticoids and IGF1 have not been studied within this weight-loss-regain paradigm so far. In addition, the modification of those systems by lifestyle modifications such as physical activity or nutrition has not yet been investigated.
Therefore, the strategic objective of this Clinical Research Unit is to identify and characterise hormonal mechanisms counterbalancing weight maintenance after a previous period of negative energy balance. The structure of the Clinical Research Unit 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.

• DFG Programme: Clinical Research Units
• International Connection: USA

Projects

• Cellular thyroid hormone signalling mechanisms during weight maintenance (Applicant Köhrle, Josef )
• fMRI-based characterization of brain activity patterns during weight loss and body weight maintenance: relation to hormonal mechanisms regulating energy homeostasis (Applicant Haynes, John-Dylan )
• Hypothalamic deep brain stimulation as a novel experimental and therapeutic approach in the treatment of adiposity (Applicant Kupsch, Andreas )
• Hypothalamic deep brain stimulation as a novel experimental and therapeutic approach in the treatment of adiposity (Applicant Spranger, Joachim )
• Interplay of peripheral circadian clocks with energy balance and body weight regulation (Applicant Pfeiffer, Andreas F. H. )
• Interplay of peripheral clock genes with energy balance and nutrients: Role of hormonal pathways (Applicant Kramer, Achim )
• Neural, hormonal and behavioral mechanisms of long-term weight maintenance (Applicant Haynes, John-Dylan )
• Novel physiological thyroid hormone metabolites as potent modulators of energy expenditure and body weight (Applicant Köhrle, Josef )
• Pharmacologic strategies for maintance of weight loss in diet induced obese mice (Applicant Wiedmer, Ph.D., Petra )
• Physical activity and body weight maintenance: What is the molecular link? (Applicant Treier, Mathias )
• Randomized controlled trial analyzing effects of a multimodal lifestyle intervention on weight maintenance in adults and children: comprehensive characterization of the variability and dynamics of mechanisms counter-balancing a period of negative energy homeostasis (Applicant Krude, Heiko )
• Randomized controlled trial analyzing long-term effects of a multimodal lifestyle intervention on weight maintenance in adults and children: comprehensive characterization of the variability and dynamics of mechanisms counter-balancing a period of negative energy homeostasis (Applicant Krude, Heiko )
• Role of pigment epithelium derived factor (PEDF) in the regulation of body weight (Applicant Birkenfeld, Andreas L. )
• Selective estrogen receptor alpha modulation during body weight cycling (Applicant Kintscher, Ulrich )
• The role of adipose tissue estrogen receptors during body weight loss and the maintenance of reduced weight (Applicant Kintscher, Ulrich )
• The role of microRNA in body weight maintenance (Applicant Rajewsky, Nikolaus )
• The role of microRNA in body weight maintenance (Applicant Rajewsky, Nikolaus )
• Z2 - administrative project (Applicant Spranger, Joachim )
• Z 2 - Verwaltungsprojekt (Applicant Grüters-Kieslich, Annette )

• Leaders: Professorin Dr. Annette Grüters-Kieslich; Professor Dr. Heiko Krude
• Spokesperson: Professor Dr. Joachim Spranger