Adipose tissue has a bad reputation. This is not least because of the increasing number of overweight and obese people worldwide. Adipose tissue cells are highly efficient energy stores that convert excess calories from food into fat deposits, often of considerable size. Nevertheless, body fat is not generally bad as it has extremely important functions. For example, as an endocrine, a hormone-producing organ, adipose tissue is involved in the regulation of many bodily processes. Researchers at the University of Augsburg and Helmholtz Munich have now succeeded in revealing another function of adipose tissue. This is because fat cells not only release hormones into the blood but also so-called extracellular vesicles.

“Extracellular vesicles are small membrane-enveloped particles that are released from all body cells and carry a kind of snapshot of cellular events through the body. They can be compared to Trojan horses that transport proteins, lipids, and nucleic acids to a target tissue for release. Once in the new cell, they can alter its function,” explains Konxhe Kulaj, PhD candidate and first author of the article. “For example, extracellular vesicles from fat cells are targeted to the beta cells of the pancreas, where they are taken up and increase the release of the hormone insulin,” Kulaj continues.

Healthy and obese adipose tissue on the move with different “cargo”

Together with doctoral candidate Michaela Bauer, her colleague Dr Alexandra Harger, and with the help of proteome researchers Dr Natalie Krahmer and Özüm Sehnaz Caliskan from Helmholtz Munich, Kulaj was able to demonstrate in a series of experiments that extracellular vesicles from healthy and obese adipose tissue carry a very different composition of messenger substances as “cargo” and thus influence the function of beta cells of the pancreas in different ways. If the extracellular vesicles originated from healthy adipose tissue, as is the case with normal weight, insulin secretion was only slightly altered. In contrast, extracellular vesicles from obese adipose tissue specifically transferred proteins and nucleic acids to the pancreas, where they greatly increased the release of insulin. As a result, blood glucose levels dropped.

Stemmer explains the significance of the results: “There is a gap in our understanding of the development of type 2 diabetes. When we are overweight or obese, for example, our body cells in muscle or adipose tissue react less sensitively to insulin; we talk about insulin resistance. In this very early stage of type 2 diabetes, our pancreas has to secrete more insulin, for example after a meal, to keep blood glucose levels in the normal range. But how do the pancreatic beta cells recognise that there is insulin resistance such that they need to provide more insulin?”

The researcher continues: “An increase in insulin secretion is very beneficial in this early stage of type 2 diabetes and leads to the body being able to maintain its blood glucose level at a normal level. Many overweight and obese people manage to do this for decades, and the disease never develops. Extracellular vesicles from the fat cells appear to play an important role in this process.”

“Overall, extracellular vesicles have great potential for application in the diagnosis and treatment of a wide variety of diseases,” says Stemmer. “Our ongoing studies aim to specifically load the vesicles to be able to use them for therapeutic purposes.”

In other studies, researchers in Augsburg and Munich are currently developing new methods for being able to use extracellular vesicles circulating in the blood for a minimally invasive investigation of organ functions. “The close networking of our Institute for Theoretical Medicine with the Augsburg University Hospital and the Helmholtz Munich Research Center creates optimal conditions for such innovative research approaches, which will ultimately serve the well-being of diabetes patients,” says Stemmer.

Original article
Kulaj et al., Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo. Nature Communications. DOI: 10.1038/s41467-023-36148-1

The research group for molecular cell biology at the Institute for Theoretical Medicine at the Medical Faculty of the University of Augsburg focuses on the development, diagnosis, and therapy of metabolic diseases, such as obesity and type 2 diabetes, as well as their possible consequences, such as diabetic nephropathy and pancreatic carcinoma. The focus of the work is on extracellular vesicles.

The newly founded Medical Faculty of the University of Augsburg, with its two main research areas “Environmental Health Sciences” (EHS) and “Medical Information Sciences” (MIS), is focused on developing a future-oriented, internationally attractive, and interdisciplinary scientific profile. With clinical centres in vascular medicine, tumor medicine, and allergology, it offers excellent opportunities for establishing networked research structures between basic scientific and clinical disciplines. With the first model medical degree programme in Bavaria, the medical faculty is developing an innovative competence-oriented, interdisciplinary, organ and topic centred training concept, in which the patient and the realities involved in the provision of care stand in focus guided by an evidenced-based, scientific approach.

Helmholtz Munich, as the German Research Center for Environmental Health, is aiming to develop personalised medicine for the diagnosis, therapy, and prevention of widespread diseases such as diabetes mellitus, allergies, and lung diseases. To this end, it investigates the interaction of genetics, environmental factors, and lifestyle. The centre’s headquarters are located in Neuherberg to the north of Munich. Helmholtz Munich employs about 2,300 people and is a member of the Helmholtz Association, which comprises 18 scientific-technical and medical-biological research centres with about 37,000 employees. www.helmholtz-muenchen.de

The German Center for Diabetes Research is one of the six German Centers for Health Research. It brings together experts in the field of diabetes research and combines basic research, epidemiology, and clinical application. The goal of the centre is to make a significant contribution to the successful, tailored prevention, diagnosis, and therapy of diabetes mellitus through a novel, integrative research approach. Members of the network are Helmholtz Munich - German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition Potsdam-Rehbruecke, the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the Eberhard Karls University of Tübingen and the Paul Langerhans Institute Dresden of Helmholtz Munich at the Carl Gustav Carus University Hospital of TU Dresden, associated partners at the universities in Heidelberg, Cologne, Leipzig, Lübeck, and Munich, as well as other project partners. www.dzd-ev.de