Research for a Future
without Diabetes

„Research for a future without diabetes – this is the mission of the DZD that inspires and unites us.“

Prof. Martin Hrabě de Angelis, DZD board member

Research for a Future
without Diabetes

"The DZD stands for research to benefit people with diabetes."

Prof. Andreas Birkenfeld, DZD-Sprecher

„The Germany-wide cooperation in the DZD ensures that multicenter studies can be carried out with the required number of participants.“

Prof. Michael Roden, DZD board member


Research for a Future
without Diabetes

„The DZD places particular importance on the fast transfer of lab results to patient care.“

Prof. Michele Solimena, DZD speaker



Research for a Future
without Diabetes

„The special feature of research at the DZD is the close interdisciplinary cooperation between different disciplines.“

Prof. Annette Schuermann, DZD Speaker

DZD - German Center
for Diabetes Research

Neuherberg, 07.03.2023

Cited1 Links Sex and Metabolic Hormones to Protect Against Obesity

Sex differences exist in the regulation of energy homeostasis, the organism’s mechanism to keep a stable body weight. Current studies indicate for instance that female mammals, including humans, are better protected against metabolic diseases during reproductive age. This is particularly important with regard to obesity, a noncommunicable disease whose prevalence has tripled since 1975 according to the World Health Organization (WHO). However, it is still not fully understood how hormones, released by sex-specific reproductive glands, signal to the brain to regulate energy metabolism in females versus males. Researchers at Helmholtz Munich pursued the question and discovered a new protein called Cited1 within hypothalamic neurons that is involved in the regulation and sensitivity of satiety pathways. The results are now published in 'Cell Metabolism'.

Obesity is a global health problem, due to its high prevalence and strong association with hypertension, coronary heart disease, stroke, and other metabolic disorders. In mammals, energy balance is maintained via a homeostatic system involving both peripheral and central systems – changes in body weight reflect an unbalanced energetic state. Studies confirmed that a clear sexual dimorphism exists in how the brain regulates energy homeostasis and in the resulting metabolic adaptation to diet-induced obesity.

Protective mechanisms of estrogens
There is growing evidence showing that postmenopausal females are more prone to develop obesity in comparison to premenopausal females. Multiple studies have established a link between the vulnerability to develop metabolic disturbances with reproductive decline. This suggests that estrogens, a category of sex hormones responsible for the development and regulation of the female reproductive system and secondary sex characteristics, play a protective role in this context. The most important estrogen hormone in females, estradiol, thereby regulates energy homeostasis by altering feeding behavior. However, how this sex hormone mediates its anti-obesity actions is still largely unknown.

“Less satiety without Cited1”
A research team led by Cristina García-Cáceres, Deputy Director and Head of the Astrocyte-Neuron Unit at the Institute for Diabetes and Obesity (IDO) of Helmholtz Munich, the German Center for Diabetes Research (DZD) and Professor at the Ludwig Maximilians University (LMU) Hospital Munich, has now discovered a novel protein named Cited1, that is highly enriched in estradiol-sensitive neurons of the arcuate nucleus of the hypothalamus, a part of the brain linking the endocrine and the nervous systems. The researchers discovered that this protein is essential for the integration of energy stores with reproductive signals for metabolic adaptation in diet-induced obesity. Using mouse models, the researchers observed that the absence of Cited1 in the hypothalamus of females weakens their capacity to respond adequately to satiety hormones such as leptin, to levels comparable with males, and thus increases their sensitivity to diet-induced obesity. This shows that Cited1 is involved in satiety signaling pathways of hypothalamic neurons, thereby contributing to the fine-tuning of food intake.

Sex differences in metabolic diseases
In this study, the researchers provide new insights that contribute to a better understanding of how neurons integrate endocrine inputs from gonadal and adipose axes via Cited1, thus contributing to the sexual dimorphism in diet-induced obesity. The study contributes to the understanding of sex differences in obesity pathogenesis and paves the way to new sex-specific anti-obesity drugs with fewer side effects to combat obesity. Further, it opens new avenues to study the role of Cited1 in the convergence of other potential neuroendocrine functions, such as puberty or growth.


Original publication:
González-García et al. (2023) Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1. Cell Metab. (In Press).


About Helmholtz Munich 
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies and chronic lung diseases. With the power of artificial intelligence and bioengineering, the researchers accelerate the translation to patients. Helmholtz Munich has more than 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH):

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Munich – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of Helmholtz Munich at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich.  

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