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Helmholtz Munich I Daniela Barreto

Kallistatin Contributes to the Beneficial Metabolic Effects of Weight Loss

Featured Publication, IDM,

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 Helmholtz Munich and the German Center for Diabetes Research (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.

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, researcher and resident physician 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, speaker of the Center for Diabetes Research (DZD), 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, Medical Director of the Department of Diabetology, Endocrinology and Nephrology at the University Hospital Tübingen.