02:20am Saturday 25 November 2017

Brown fat behind increased cardiac death rate in winter

It has long been known that the number of deaths caused by cardiovascular disease increases when it is cold during the winter months. It has been speculated that the increase may be due to shovelling snow and limited physical activity, but the underlying mechanism remains unclear. The current study, published in the journal Cell Metabolism, demonstrates a new principle for how the cold increases the risk of arteriosclerosis (also called hardening of the arteries or fattening of the arteries) – the result of a collaboration between researchers from the two Swedish institutions and three universities in China.

The researchers studied mice that had been genetically altered so that they had a higher propensity for arteriosclerosis. Mice, like humans, have both white and brown fat in the body. Rolls of fat are comprised mostly of white fat, where the body stores excess calories. Brown fatty tissue, on the other hand, can burn fat to generate heat. The process is activated by the cold and has been regarded as being beneficial to health.

Professor Yihai Cao“From the start, we believed that the activation of brown fat by the cold would simply make the mice thinner and healthier. Instead, the fatty deposits in the blood vessels increased, which was very surprising and contrary to what we had believed”, says Yihai Cao (pictured), professor at the Department for Microbiology, Tumor and Cell Biology at Karolinska Institutet and in the Department of Medicine and Health Sciences at Linköping University.

It turned out that when the mice were exposed to the cold, it accelerated the formation of arteriosclerotic plaque, which can cause heart attacks and cerebral haemorrhaging. In addition, the plaque was rendered less stable by the cold. If arteriosclerotic plaque ruptures, the stored fat can leak out into the blood and block the blood vessels in the heart and brain. The cold-activated breakdown of fatty acids in the brown fat of the mice resulted in an accumulation of the “bad” LDL cholesterol in the blood and increased the amount of fat stored in the plaque.

“If this turns out to be the same for humans as well, it is reasonable to recommend that people who suffer from cardiovascular diseases should try to avoid exposure to cold and wear warm clothes when they are outside in winter”, says Cao.

Researchers hope to be able to further develop the results with studies in humans.

“It would be incredibly significant if it works in the same way in humans. Brown fatty tissue is not only affected by the cold, but activation can be blocked by several existing medications, which is something we want to study further”, says Cao.

It was long believed that humans only had white fatty tissue, and that brown fat only occurred in some mammals – rodents, for example. Years later, research showed that humans seemed to have two different types of brown fatty tissue. Recently, researchers from Sweden and other countries demonstrated that infants – at the least – have the typical brown, heat-forming fatty tissue, a discovery which raised hopes of new ways of treating being overweight. However, the current study indicates that there may be risks involved with activating brown fatty tissue to reduce body weight in people who also suffer from any form of cardiovascular disease.

The study has been financed with grants from organisations such as the Swedish Research Council, the Swedish Cancer Society, Torsten Söderbergs Stiftelse, the European Research Council (ERC) and the EU’s seventh framework programme through the research project METOXIA. The three Chinese universities that participated in the collaboration were Shandong University, Tianjin Medical University and Sun Yat-Sen University.

Article: Cold exposure promotes atherosclerotic plaque growth and instability via UCP1 dependent lipolysis by Mei Dong, Xiaoyan Yang, Sharon Lim, Ziquan Cao, Jennifer Honek, Huixia Lu, Cheng Zhang, Takahiro Seki, Kayoko Hosaka, Eric Wahlberg, Jianmin Yang, Lei Zhang, Toste Länne, Baocun Sun, Xuri Li, Zhiyi Liu, Yun Zhang and Yihai Cao, Cell Metabolism, 2 July 2013.

Website of the journal: www.cell.com/cell-metabolism

Contact:
Yihai Cao, professor, +46(0)8-524 875 96, +46(0)70-559 75 96, yihai.cao@ki.se


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