KFO 218: Hormonal Regulation of Body Weight Maintenance

肥胖是挑战全球卫生保健系统的最普遍疾病之一，因为它对肥胖者的发病率、死亡率和生活质量有着巨大的影响。各种各样的策略，包括生活方式和药物方法，已被证明可以在短期内支持或诱导体重减轻。然而，这些策略通常不能在一个新的设定值上建立持续的能量平衡，也不能长期稳定体重。相反，许多个体恢复体重的速度相对较快，干预后的体重甚至比基线体重增加（体重循环），这一现象在并发症方面可能比肥胖本身更糟糕。肥胖个体的体重减轻与减少能量消耗的矛盾反调节有关。最近的研究表明，激素机制对这一现象起着重要作用。这种协调的激素反应有利于体重恢复，因此对长期维持体重非常重要。有机会改变体重恢复的内分泌成分意味着治疗干预，以提高体重维持的成功。为了将这些发现转化为以激素为基础的维持体重的临床治疗试验，需要对减肥过程中这些反调节内分泌反应进行更详细和个性化的调查。进一步的内分泌反应，如性类固醇、糖皮质激素和IGF1，到目前为止还没有在这种减肥恢复模式中进行研究。此外，通过改变生活方式（如体育活动或营养）来改变这些系统尚未得到调查。因此，该临床研究单位的战略目标是确定和描述在前一段时间的负能量平衡后平衡体重维持的激素机制。临床研究单位的结构利用了柏林/波茨坦地区内分泌学和能量稳态主题的临床和基础研究专业知识，并促进了将实验结果转化为治疗方法，从而改善了体重维持和代谢健康。

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.