Hope for the overweight

12-Aug-2014 - Germany

The body has different types of adipose tissue that perform various metabolic tasks: white, beige and brown. For the first time, researchers at the Helmholtz Zentrum München and Harvard Medical School have successfully identified specific surface proteins that can help distinguish between the three types. This discovery makes it possible to develop new treatment options for adiposity. The work has been published in Science Translational Medicine.

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.

The good and the bad side of fat

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.

New hope to finally let fat melt away

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."

Original publication

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

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Original publication

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

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