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Brown fat cells are therapeutic target for weight-loss

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(Vienna, 07 September 2018) In most cases, being seriously overweight leads to secondary diseases such as diabetes, cardiovascular disease and cancer. That is why the best option for avoiding obesity and its consequent diseases is to prevent people from gaining weight. Scientists from MedUni Vienna, the Max Planck Institute for Metabolic Research in Cologne and Syddansk University in Odense, Denmark, are therefore currently investigating the function and regulation of brown fat cells, since these burn a lot of calories and are therefore the ideal endogenous cells to consider when it comes to options for weight reduction. The outcome: activation of brown fat cells and the special genes they contain could help with weight loss.

In humans and mammals, a distinction is generally made between at least two types of fatty deposits, white and brown adipose tissue. White adipose tissue occurs much more frequently in the human body, stores fat and is predominantly located in the well-known fatty pads on the abdomen, bottom and upper thighs. When the body needs more energy, it can call upon these stores. In contrast, brown fat burns energy, releasing heat, which is why babies, for example, have a lot of it. However, after the neonatal stage and when people are overweight, the number of these cells steadily declines.

"Brown adipose tissue was identified as an option for helping people lose weight, because it is able to burn a lot of calories," explains Elena Schmidt, who works as a PhD student in Jan-Wilhelm Kornfeld's research group in Cologne. Just 40 – 50 g of brown fat cells could burn 20% more  calories. "Activating brown fat cells is therefore a novel option for losing weight without any side-effects,” adds Martin Bilban from the Department of Laboratory Medicine at the Medical University of Vienna.

The two research teams led by Bilban and Kornfeld have therefore been concentrating on a little-researched aspect of brown fat cells. So-called long, non-coding RNAs (LncRNAs), have only recently been discovered and act in a very tissue-specific way in the cells, giving them great potential as candidates for therapeutic approaches.

They found one LncRNA, H19, that plays an important role in the formation and function of brown fat cells. The scientists were able to show in a mouse model that high H19 activity prevented the mice from putting on weight. "We were surprised to see that, even with a high-fat diet, the mice with high H19 activity hardly put on any more weight than their healthy counterparts,” reports Bilban.

The researchers also discovered another peculiarity. H19 controls a very rare class of genes, which, in contrast to most genes in humans and mice, are only inherited from one parent (i.e. either the mother or the father). "One result of our research was that we were able to observe that paternal genes are more likely to lead to obesity, while their maternal counterparts ensure that the offspring remain slim," explain the researchers, while Kornfeld adds, "We think that we are on the trail of the underlying mechanism, whereby paternal and maternal genes engage in a sort of tug-of-war in the offspring's genetic material. This is where our work really starts."

Service: Nature Communications
„LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat.“ Elena Schmidt, Ines Dhaouadi, Isabella Gaziano, Matteo Oliverio, Paul Klemm, Motoharu Awazawa, Gerfried Mitterer, Eduardo Fernandez-Rebollo,Marta Pradas-Juni, Wolfgang Wagner, Philip Hammerschmidt, Rute Loureiro, Christoph Kiefer, Nils R. Hansmeier, Sajjad Khani, Matteo Bergami, Markus Heine, Evgenia Ntini, Peter Frommolt, Peter Zentis, Ulf Andersson Ørom, Jörg Heeren, Matthias Blüher, Martin Bilban*#, Jan-Wilhelm Kornfeld*# (*Diese Autoren haben die Studie gemeinsam geleitet; #Korrespondenz). Nature Communications 2018 Sept6th, DOI: 10.1038/s41467-018-05933-8.