12-Nov-2019 - Boehringer Ingelheim Stiftung

Deciphering how the brain controls our weight

Jens Brüning receives 2019 Heinrich Wieland Prize

Professor Jens Brüning, Director at the Max Planck Institute for Metabolism Research in Cologne, Germany, has been honoured with the 2019 Heinrich Wieland Prize for his pioneering work on how the brain regulates the uptake, storage, and use of energy in the body. He has shown that certain brain centres – and, in particular, their interplay with the hormone insulin – are central to the control of body weight. He received the Prize, endowed with 100,000 Euros by the Boehringer Ingelheim Foundation, at a scientific symposium on 7 November in Munich.

According to the World Health Organization, more than a third of all adults worldwide are overweight, and this proportion has risen sharply in recent decades. In most people’s experience, gaining weight is easy; losing it is hard. Many still think it only requires willpower. And, while much of weight gain or loss is decided in the brain, research shows that biology is a key factor. Thanks to Jens Brüning’s work, we now know that the brain controls our metabolism through a finely tuned system of hormones, the signals that control them, and particular clusters of nerve cells. He has identified some of the important players, where they are located in the brain, and how they act together in both healthy and diseased people.

“Jens Brüning is one of the world’s leading researchers of how the brain regulates the metabolism of energy in our body. Over the past 20 years, his pioneering research has laid much of the groundwork for identifying the brain as the master regulator of energy metabolism and for unveiling the brain’s tight rein on blood sugar levels and its control over appetite and body weight”, says Professor F.-Ulrich Hartl, chairman of the Award’s selection committee. Professor Michael Manns, member of the Executive Committee of the Boehringer Ingelheim Foundation adds: “Professor Brüning’s work holds great promise for millions of people suffering from diabetes, for instance. It is also a prime example of just how important basic research is for the progress in medicine”.

In one of his earliest, widely recognized studies, Brüning and his team developed the first genetically altered mouse strain for the study of type 2 diabetes. Diabetes develops when cells no longer react to insulin or when insulin production is impaired. Insulin is central to controlling blood sugar levels, as it is the only hormone able to lower the blood level of glucose, the simple sugar the body uses as its energy currency. In healthy people, blood sugar levels stay within a certain range, yet fluctuate constantly – rising sharply when we eat and dropping quickly when we exert ourselves heavily. After a meal, a large proportion of glucose entering the blood stream is normally taken up by muscle cells for more or less immediate use. Excess sugar is taken up by the liver, which converts it into fat for long-term storage. Too much or too little glucose – as happens in diabetes patients – can lead to unconsciousness, serious lasting damage, or even death.

Brüning was the first to switch off the receptor for insulin in specific tissues, such as muscle, the liver and the brain. This, in turn, enabled him to monitor more closely than ever before how and where insulin acts. It was long thought that the cause of diabetes and other metabolic disorders was to be found within the body’s periphery, for example in its muscles, liver, or pancreas. However, Brüning’s studies showed a much more comprehensive role of insulin than was previously thought possible, involving complex feedback mechanisms in the brain.

For example, he was the first to show the central role of only about 3,000 so-called AgRP cells in the hypothalamus, a region of the brain important for many of the body’s hormonal processes. Using pioneering techniques, he showed that this group of nerve cells is responsible for how much we eat and how much glucose the liver releases by converting fat back into sugar. These cells also regulate how sensitively our body’s cells react to insulin. In addition, he discovered that they cease to react to insulin in the case of obesity. They are said to become insulin-resistant, and can no longer function properly. His extensive research of the AgRP cells provided the basis for new approaches to develop drugs to treat obesity caused by insulin resistance.

More recently, Jens Brüning found evidence in mice as to why the children of obese mothers may face a higher risk of developing diabetes or obesity, a long-known phenomenon. He found that in the brains of baby mice whose mothers were on a high-fat diet during the suckling period, the circuits of nerve cells that normally suppress appetite did not develop normally. As this period in mice is comparable to the last trimester of human pregnancy, these findings further underscore the direct relevance of Jens Brüning’s basic research to individuals and society, as a whole.

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