After weight loss, people with overweight and obesity express more of the protein Kallistatin* in subcutaneous white adipose tissue. This was demonstrated by researchers from the DZD in a recent study. In addition, Kallistatin improves metabolism and could open up new therapeutic options for people with obesity and type 2 diabetes in future. The results have now been published in ‘Molecular Metabolism.’

An increasing number of people are developing type 2 diabetes and obesity. These are highly complex and multifaceted diseases. In order to treat them sustainably, new approaches to therapy are needed. Clinical studies on humans have shown that heavily overweight individuals produce less Kallistatin. Kallistatin is a protein that has various effects in the body. Among other things, it is involved in counteracting inflammation and healing wounds. The role that Kallistatin plays in glucose metabolism and its potential suitability as a therapeutic target are currently being investigated by researchers from the German Center for Diabetes Research (DZD), the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the Eberhard-Karls-University of Tübingen, and the Department of Diabetology, Endocrinology and Nephrology at the University Hospital Tübingen.

Kallistatin Expression Increases After Weight Loss
To this end, they measured Kallistatin expression in subcutaneous white adipose tissue in 47 individuals with overweight to obesity before and after weight loss. The result: Kallistatin expression increases after weight loss.

Kallistatin Improves Hepatic Insulin Sensitivity
Additionally, the researchers examined the effect of the protein in an animal model. In the process, they observed that human Kallistatin improves hepatic insulin sensitivity in diet-induced obese mice.

“Our results suggest that Kallistatin may be an interesting, yet challenging, therapeutic target for people with obesity and insulin resistance,” says lead author Leontine Sandforth. “Because Kallistatin has insulin-sensitizing effects in the liver, it should be investigated as a potential liver-specific target for emulating the beneficial effects of weight loss and potentially treating type 2 diabetes and obesity,” adds last author Prof. Andreas Birkenfeld.

Expression of the protein Kallistatin increases after weight reduction. In mice, it improves hepatic insulin sensitivity. © IDM, support@biorender.com.

The Most Important Results at a Glance

• Kallistatin is expressed in human subcutaneous white adipose tissue.
• Kallistatin mRNA expression in subcutaneous adipose tissue increases in people with overweight and obesity after weight loss.
• Human Kallistatin improves hepatic insulin sensitivity in diet-induced obese mice.
• Kallistatin may contribute to the beneficial metabolic effects of weight loss.

*Kallistatin (KST)
Kallistatin is a circulating, broadly acting human protein. It plays a role in healing injuries and preventing illnesses, for example. Clinical studies in humans revealed reduced KST levels in obesity. However, the exact role of this protein in the regulation of blood sugar and energy metabolism in the setting of insulin resistance and type 2 diabetes is not yet fully understood. Researchers are working to decode these relationships in order to find new approaches for treating metabolic disorders.

Original publication:
Leontine Sandforth… Andreas L. Birkenfeld: Role of human Kallistatin in glucose and energy homeostasis in mice, Molecular Metabolism,Volume 82, 2024. DOI: doi.org/10.1016/j.molmet.2024.101905.

About the researchers:
Leontine Sandforth
The researcher and resident physician works at DZD partner the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the Eberhard-Karls-University of Tübingen and at the Department of Diabetology, Endocrinology and Nephrology at the University Hospital Tübingen.

Prof. Dr. med. Andreas Birkenfeld
The speaker of the Center for Diabetes Research (DZD) is head of the DZD site in Tübingen, the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the Eberhard-Karls-University of Tübingen. He is the Medical Director of the Department of Diabetology, Endocrinology and Nephrology at the University Hospital Tübingen.

Scientific Contact:
Prof. Dr. med. Andreas Birkenfeld
Telefon: 07071 29-82735
E-Mail: andreas.birkenfeld@med.uni-tuebingen.de

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): www.helmholtz-munich.de/en     

Founded in 1805, Tübingen University Hospital is one of the leading centers of German university medicine. As one of the 33 university hospitals in Germany, it contributes to the successful combination of high-performance medicine, research and teaching. Well over 400,000 inpatients and outpatients from all over the world benefit annually from this combination of science and practice. The clinics, institutes and centers unite all specialists under one roof. The experts work together across disciplines and offer each patient the best possible treatment based on the latest research findings. Tübingen University Hospital conducts research for better diagnoses, therapies and healing chances; many new treatment methods are clinically tested and applied here. In addition to diabetology, neuroscience, oncology, immunology, infection research and vascular medicine are research priorities in Tübingen. The Department of Diabetology /Endocrinology has been the center of interdisciplinary research over the past 25 years, especially with the participation of surgery, radiology and laboratory medicine. This important discovery of the prediabetes subtypes was only possible due to the interdisciplinary collaboration between the hospital’s various departments. Tübingen University Hospital is a reliable partner in four of the six German Centers for Health Research initiated by the German Federal Government. www.medizin.uni-tuebingen.de 
 

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. www.dzd-ev.de/en