The 2014 Zülch Award – weighty award for medical doctors

Stephen O’Rahilly and Jeffrey M. Friedman investigate the causes of obesity

September 10, 2014

Obesity is very much in the genes – that is the surprising finding of biomedical research in recent years. The Gertrud Reemtsma Foundation has bestowed the 2014 Zülch Award on two doctors who have rendered outstanding services to research into metabolic diseases. Jeffrey M. Friedman identified the hormone leptin and found that it plays a key role in controlling food intake, body weight and many other physiologic processes. Sir Stephen O'Rahilly recognized that human obesity can be a hereditary disorder and identified a number of causative gene mutations. With their findings, both have helped to ensure that overweight and obesity states are no longer stigmatised as being due to a weak will or lack of discipline. The award will be presented in Cologne on 12 September 2014.

The ranks of overweight people are increasing so dramatically worldwide that experts are now talking of an epidemic. More than half of adults in Germany are overweight, and nearly a quarter are considered obese. The proportion of overweight people is also rising dramatically in many emerging countries. It is often thought that this is a result of a modern lifestyle with calorie rich and excessively rich food although this does not explain why some people are obese and others are lean. Thus while diet and exercise appear to be important in controlling body weight, it has long been evident from studies of twins and of adopted children that genetic factors play a major role in influencing an individual’s susceptibility to becoming obese.

Jeffrey M. Friedman has extensively investigated the role of leptin and discovered that it keeps fluctuations in energy reserves within narrow limits. Leptin is produced by the body’s fat cells, which release the hormone into the bloodstream. The quantity released mirrors the available fat reserves: If the fat proportion is high, up to 100 times more leptin is secreted. As a result, body weight decreases. Conversely when fat mass falls, leptin levels go down which in turn stimulates appetite. When the researchers administered the hormone to mice lacking the leptin gene, the animals lost their appetite, and their blood sugar levels and body weight fell.

The target of leptin is the brain – the hypothalamus to be precise. Within the hypothalamus Friedman discovered nerve cells carrying a receptor for leptin. When the hormone binds to this receptor, it alters the wiring of nerve cells that control eating behaviour, also diminishing the sense of pleasure associated with eating.

Thanks to research by Sir Stephen O'Rahilly and his colleagues, we are now aware of a number of hereditary metabolic disorders causing obesity and diabetes that are due to specific genetic mutations. He has shown, for example, that mutations in the leptin and melanocortin-4-genes can cause massive obesity in human patients. Overweight and obesity states can therefore be due to a single gene mutation.

Many of those genes are active in nerve cells in the brain, where they regulate neural activity and control eating behaviour. It is now recognized that obesity can be identified as a hereditary disorder that is modulated by external factors such as diet and exercise – a finding that O'Rahilly was instrumental in bringing about.

The discovery of leptin in the mouse by Friedman and O’Rahilly’s demonstration that it plays a similar role in humans can be regarded as one of the most important breakthroughs in metabolic research since the discovery of insulin. It has meanwhile led to new forms of treatment. For example, leptin is now used to treat patients with lipodystrophy, which can result in a severe form of diabetes.

Jeffrey M. Friedman was born in Orlando, Florida and studied medicine in Albany, New York state. Mr. Friedman is researching and teaching at Rockefeller University and the Howard Hughes Medical Institute in New York. Sir Stephen O’Rahilly is also a medical doctor and hails from Ireland, where he studied at the National University of Ireland in Dublin. Since 2002, he has been Professor for Clinical Biochemistry and Medicine at Cambridge University, UK and has also headed various research projects at the university-affiliated Addenbrooke’s Hospital.

The 2014 K.J. Zülch Award ceremony will be held in the Hansa Room of Cologne’s historical town hall from 10:00 a.m. to 12.00 on 12 September. Following a laudatory speech by Jens Brüning from the Max Planck Institute for Metabolism Research in Cologne, Stephen O’Rahilly will report on Leptin and the basis of obesity. Matthias H. Tschöp from the Helmholtz Zentrum München will hold the laudation for Jeffrey M. Friedman. The laureate will then talk about obesity as a heritable disorder of the central control of energy balance.


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