Macrophages leave brown adipose tissue cold

Brown adipose tissue is considered a pharmacologically interesting target structure to treat obesity. When the "good" brown fat is activated, the metabolism is boosted, and the "bad" white fat deposits are broken down. Scientists led by Dr. Timo Müller of Helmholtz Zentrum München, Institute for Diabetes and Obesity (IDO) and a partner in the German Center for Diabetes Research (DZD), have now shown that macrophages do not activate this process, as previously thought. Their paper has now been published in 'Nature Medicine'.

Brown adipose tissue generates heat through the oxidation of fatty acids. It is found not only in newborns, but to a certain extent also in adults. This makes cells of brown adipose tissue an interesting target structure for pharmacotherapies for obesity. Up to now, scientists thought that heat generation in the brown fat would also be activated via norepinephrine production in certain immune cells, so-called macrophages.

“We have now been able to disprove this existing dogma," said Katrin Fischer, PhD student at the Institute for Diabetes and Obesity, Helmholtz Zentrum München. Together with Dr. Timo Müller, head of Pharmacology at the IDO, she showed in the model that certain immune cells have no influence on thermogenesis. "So-called M2 macrophages * are not capable of synthesizing norepinephrine," Müller added. “They do not have the necessary key hormone, tyrosine hydroxylase.”

Through their experiments, Fischer and Müller showed that attempts to activate brown adipose tissue via M2 macrophages did not lead to success. Various pharmacotherapies aim to activate oxidative processes to treat obesity. The worldwide search for suitable molecules continues. The studies, which have been published in the renowned journal Nature Medicine, are part of a large-scale international collaboration, in particular with Prof. Christoph Buettner of the Icahn School of Medicine at Mount Sinai, New York.

Further Information

Original Publication:
Katrin Fischer et al. (2017), Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nature Medicine, doi:10.1038/nm.4316. Abstract...

In addition to the Institute for Diabetes and Obesity (IDO) of Helmholtz Zentrum München, The Mount Sinai Diabetes, Obesity and Metabolism Institute (DOMI) at the Icahn School of Medicine, New York, was also involved, among others.

*Macrophages are cells of the immune system. M1 macrophages promote inflammation, while those that reduce inflammation and promote tissue repair are called M2 macrophages. This difference is reflected in their metabolism. M1 macrophages have the ability to synthesize nitric oxide from arginine while M2 macrophages have the unique ability to produce the "repair molecule" ornithine from arginine.