Hope for the overweight

White, brown and beige adipocytes, or fat cells, are inherently different. Each of these cell types has different functions and each plays its own role in metabolism. In the human body, white adipose tissue is by far the most prevalent. Its primary function is energy storage. On the other hand, brown adipocytes utilize available energy to generate heat but are only found in a few places in the adult human body. Beige adipocytes, which represent a special type of brown adipocytes, appear mixed with brown adipocytes in human brown adipose tissue or develop within the white adipose tissue, particularly under the influence of cold in rodents.

A team of researchers headed by Dr. Siegfried Ussar from the Institute for Diabetes and Obesity (IDO) at the Helmholtz Diabetes Center/ Helmholtz Zentrum München, partner of the German Center for Diabetes Research (DZD), and Professor C. Ronald Kahn from the Joslin Diabetes Center and Harvard Medical School has now succeeded in very specifically distinguishing the various adipocytes on the basis of their surface proteins. This is raising hope for a new method to treat those suffering from obesity and diabetes.

Rapidly growing rates of obesity result in increasing rates of type 2 diabetes and other components of the metabolic syndrome. To ameliorate the consequences of excessive caloric intake and storage, modern medicine is seeking new ways to enhance energy expenditure to reduce body weight. "Because of its function as the body's thermal power station, brown adipose tissue has the ability to burn large quantities of energy that otherwise would be stored in white adipose tissue as fat," says first author Siegfried Ussar. For this reason, activation of brown adipose tissue using drugs offers an attractive approach to treat obesity and the illnesses that result from it, such as type 2 diabetes.

The amount of brown adipose tissue varies greatly from individual to individual, and until now it was not possible to determine its proportion reliably. Current methods are based on measuring this tissue's activity, which greatly depends on outside conditions, such as the temperature or diet. The newly discovered surface proteins now offer an activity independent approach. They additionally make it possible to selectively deliver substances to brown adipose tissue by targeting these proteins.

Activation of the brown adipose tissue is currently one of the most promising approaches to battling adiposity,* opening up new avenues to reduce excess weight without reducing the calorie intake. This is why numerous publications from basic research describe new potential mechanisms to activate or propagate the human brown adipose tissue. "Translating these research results into practice often fails, however, because the identified mechanisms also have important functions in other organs, which can result in incalculable side effects," Dr. Ussar explains. "Our research represents a novel approach to this problem, because the surface markers that we have discovered are very specific for the individual fat types and independent of the metabolic activity."

The scientists hope that further development of their research results will allow to introduce active substances selectively into the brown adipose tissue and consequently reduce side effects. "We are already at work, partially in our own group and also in collaboration with other groups at the Helmholtz Zentrum München, to produce specific molecules that recognize these surface proteins to examine their efficacy," Dr. Ussar reports. "Our goal is to work with partners from industry to further develop these molecules for use in humans."

*Adiposity: Also called obesity; this is a nutritional and metabolic disease with significant excess weight that is characterized by an increase in the body fat that goes beyond the normal measure with pathological effects. As a rule, it is caused by overeating and lack of exercise and is promoted by genetic factors. Obese patients also are more likely to suffer from type 2 diabetes.

Ussar, S. et al. (2014). ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipo-cytes, Science Translational Medicine, doi: 30 July 2014, Vol. 6, Issue 247, p. 247ra103, DOI: 10.1126/scitranslmed.3008490

Link to publication

More information, including a copy of the paper, can be found online at the Science Translational Medicine press package at http://www.eurekalert.org/jrnls/scitransmed

As German Research Center for Environmental Health,Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,100 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members.

The German Center for Diabetes Research e.V. brings together experts in the field of diabetes research and combines basic research, epidemiology and clinical applications. The members of the association are the German Diabetes Center (DDZ) in Düsseldorf, the German Institute of Human Nutrition (DifE) in Potsdam-Rehbrücke, the Helmholtz Zentrum München – the German Research Center for Environmental Health, the Paul Langerhans Institutes of the Carl Gustav Carus University Hospital in Dresden and the Eberhard Karl University of Tübingen as well as the Gottfried Wilhelm Leibniz Research Association and the Helmholtz Association of German Research Centers. The aim of the DZD is to find answers to unsolved questions in diabetes research by adopting a novel, integrative approach and to make a significant contribution towards improving the prevention, diagnosis and treatment of diabetes mellitus.

TheInstitute for Diabetes and Obesity (IDO) erforscht die Erkrankungsmechanismen des Metabolischen Syn-droms mit systembiologischen und translationalen Ansätzen. Mittels zellulärer Systeme, genetisch modifizierter Mausmodelle und klinischer Interventionsstudien sollen neue Signalwege und Zielstrukturen entdeckt werden. Ziel ist die interdisziplinäre Entwicklung innovativer Therapieansätze zur personalisierten Prävention und Behandlung von Adipositas, Diabetes und deren Begleiterkrankungen. Das IDO ist Teil des Helmholtz Diabetes Center (HDC).

Communication Department, Helmholtz Zentrum München- German Research Center for Environmental Health (GmbH), Ingolstaedter Landstr. 1, D-85764 Neuherberg, phone: 0049 89 3187 2238, e-mail: presse@helmholtz-muenchen.de

Dr. Siegfried Ussar, Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Institute forDiabetes and Obesity, Ingolstädter Landstr. 1, D-85764 Neuherberg - Tel. 0049 89-3187-2047, e-mail: siegfried.ussar@helmholtz-muenchen.de