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Some Kinds of Fat Worse Than Others - Abdominal Fat Decisive Factor - International Symposium at the MDC

27.10.2005 - (idw) Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch

Some kinds of excess fat are worse than others. Until very recently, all overweight or obese people were considered to be at high risk for developing type 2 diabetes and high blood pressure which can lead to stroke, heart attack, and kidney damage. Now, based on new insights, the medical community has a more differentiated view of obesity. It is not so much the Body Mass Index (BMI) that is the decisive factor, but rather where on the body the excess fat is distributed. Particularly dangerous is stoutness around the waist and abdomen, which used to be described with the euphemism "portliness" and was considered a sign of prosperity. Doctors refer to this as "abdominal obesity". People with this form of overweight are especially prone to develop secondary diseases of obesity early on. This is one of the newest findings that was presented at the 4th International Symposium on Obesity and Hypertension at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. The symposium from October 27 -29, 2005, in which 200 experts from Europe, North and South America and Asia participate, is organized by Professor Arya Sharma (McMaster University, Hamilton, Ontario, Canada) and Professor Friedrich Luft (Franz Volhard Clinic, Charité University Medical School Berlin/Helios Clinics Berlin-Buch and the MDC). Researchers already established years ago that fat cells produce a multitude of substances which directly damage the cardiovascular system and the kidneys. Recently, they discovered that the fat cells of the abdominal tissue are especially active metabolically and are, therefore, especially dangerous. They produce hormones and messenger substances (adipokines) that greatly contribute to the development of hypertension and metabolic disorders, such as type 2 diabetes and elevated blood lipid levels. Doctors use the collective term "metabolic syndrome" when referring to these diseases.

By contrast, the Body Mass Index (BMI), which is calculated by dividing the body weight in kilograms by height in meters squared, says nothing about fat distribution. According to the World Health Organization (WHO), a person with a BMI of more than 25 kg/m² is considered overweight; whereas a person with a BMI of 30 kg/m² or more is considered obese. For example, a man who is 1.8 m tall and a weight of 81 kg has a BMI of 25 kg/m²; with a weight of 97 kg, his BMI would be over 30 kg/m². "The BMI remains the standard for determining whether someone is really too fat. However, doctors should pay attention to fat distribution as well," Professor Sharma emphasized at the symposium in Berlin.

WHO: A Billion People Overweight - Europe Catches Up with the US
Overweight and obesity have become a worldwide problem over the past years, affecting not only the population of rich industrial countries but also those living in so-called developing and threshold countries as well. In such countries, abundance and hunger often co-exist. According to UN statistics, 6.5 million people died of hunger and associated secondary diseases in 2005 alone. By contrast, the World Health Organization estimates that worldwide a billion people are overweight and more than 300 million are obese. In Germany, 16 million people are too heavy which corresponds to 20 percent of the population. In fact, according to a 2002 international health survey, 75 percent of 25 year old German men are considered to be too fat. In this respect, they were only surpassed by like-aged Greek men, who topped the European chart at 78 percent. These two countries, together with Finland, Malta, Slovakia, the Czech Republic and Cyprus, even surpass the US as far as weight is concerned where 67 percent of the male population is considered to be too fat. The European Union (EU) estimates that between two and eight percent of the medical costs in the EU are spent for the treatment of overweight and obesity. In the spring of this year, the EU therefore launched an action platform to meet this challenge.

Shortened Life Expectancy
Scientists and doctors fear that overweight and obesity are threatening to shorten the dramatically increased life expectancy that has evolved over the last decades as a result of a sufficient food supply, among other factors. The increasingly urban lifestyle combined with insufficient exercise and sedentary lifestyle, an excess in overall food consumption, as well as an excess of consumption of high fat foods has led to the situation that people no longer work off their excess pounds. According to the WHO, around 250,000 people die every year in Europe alone from cardiovascular diseases as a consequence of being overweight and worldwide two to five million people die due to these factors.

High Blood Pressure and "Adult Onset Diabetes" Already in Children
Scientists and doctors observe with concern that even children and adolescents are increasingly overweight and that they suffer from "adult onset diseases" early in life such as high blood pressure and even type 2 diabetes. The WHO assumes that worldwide 18 to 22 million children under five years of age are too fat. In Europe, one in five children is considered to be too fat and every year more than 400,000 overweight schoolchildren join these ranks. According to the International Obesity Task Force, the curve is steepest for children in England and Poland. Of the estimated 14 million European children who are overweight, three million are considered obese.

It is to be feared that these children are not only less healthy than their parents but that they also will have a shorter life expectancy, as Professor Jan Olshansky from the School for Public Health at the University of Illinois in Chicago warned recently in the New England Journal of Medicine. Indeed, studies from Iran, Croatia, and Poland that were presented at the symposium in Berlin show that overweight or obese children and adolescents already suffer from hypertension and type 2 diabetes.

According to a study at the University of Hamedan, Iran, overweight children have a 50 percent higher risk of suffering from high blood pressure than other children of the same age with normal weight. The doctors examined more than 1,000 school children aged six to eleven years. Doctors in Croatia, who performed medical check-ups on almost 800 children in Zagreb and Koprivnica, arrived at a similar conclusion, as did their colleagues in Poland. They are therefore demanding better education, starting at an early age, to teach children healthy nutrition.

Losing Weight - Easier Said Than Done
Lose weight and, most important, get rid of abdominal fat - that is what doctors recommend. It is the most effective way to reduce blood pressure and the risk for secondary diseases. But most patients do not succeed in losing weight and keeping it off. In a short time, most of the patients regain the pounds that took them such an effort to loose. Professor Sharma defends the patients: "It is too simple to make the patients alone responsible for this lack of success. Genetic factors play a role in the regulation of bodyweight, as do the fat cells themselves. Frequently, too, medications for blood pressure and diabetes make losing weight more difficult."

The following pages are e m b a r g o e d until Saturday, October 29, 2005 at 11:00 a.m.
New Kind of Appetite Suppressant - Hope for the Obese?
A possible alternative could be an entirely new substance group which simultaneously blocks feelings of hunger and reduces blood lipid levels, thereby reducing the risk for cardiovascular diseases and type 2 diabetes. The new drug, called Rimonabant, has few side effects. It intervenes exactly where the body controls the hunger feeling, namely in the endocannabinoid system (ECS). Endocannabinoids are the body's own substances similar to cannabis (hashish), which are released upon feelings of stress, hunger, and pain, as Vincenzo di Marzo explained in Berlin. He is a professor at the Institute for Biomolecular Chemistry of the Italian Research Council in Pozzuoli. Endocannabinoids also play a role in the intricate regulation of the cardiovascular system.

Up to now, particularly two endocannabinoids were known - one of them is anandamide. The name originates from Sanskrit and means "bliss". According to Vincenzo di Marzo, the system was discovered during research on how cannabis (hashish) works, which gave the system its name. When hungry, the organism releases increased amounts of anandamide, he continued. This is in line with the known fact that hashish users frequently have attacks of the "munchies".

Endocannabinoids bind and activate two cannabinoid receptors. In particular, cannabinoid receptor1 (CB1) is of great interest to research and medical practice. CB1 is mainly found in the brain, in different organs, and in fatty tissue. According to Professor di Marzo "[CB1] is obviously primarily responsible for food intake after a starvation period. It sees to it that fat is deposited in the fat cells." This is how the body creates fat reserves in order to survive hunger periods better.

Experiments with obese lab rats have shown that, the more they eat, the more endocannabinoids bind to the CB1-receptor, which is hyperactive in these animals. The result: The binding of endocannabinoids to CB1 increases appetite, Professor George Kunos demonstrated. He is from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), which is part of the National Institutes of Health (NIH) in Bethesda, Maryland, USA. Furthermore, Professor Kunos, who had to cancel his presentation in Berlin, was able to show in experiments with mice that blocking this receptor with the substance rimonabant reduces appetite. The animals become thin and stay that way despite being offered an overabundance of food. And rimonabant not only reduces the animals' weight but also their blood pressure.

RIO in Europe - Clinical Studies
For over two years rimonabant has been tested in clinical trials. Director of the RIO (Rimonabant in Obesity) clinical trial in Europe is the diabetologist and metabolism expert Professor Luc Van Gaal of the University Hospital in Antwerp, Belgium. Included in the trial are 1,507 patients from 60 clinics in Belgium, Germany, Finland, Sweden, the Netherlands, and the US with a BMI of over 30 kg/m2 and of over 27 kg/m2 who additionally have high blood pressure and elevated blood lipid levels. The RIO trial is one of a total of four Phase III trials (testing effects and side effects in a larger number of patients) with 6,600 patients. The patients were put on a diet and also had to complete an exercise program. They were divided into three groups: the first group received 20 mg of rimonabant daily, the second group received 5 mg, a day and the third group received a placebo.

Reduces Bodyweight and Improves Metabolic Parameters
As Professor Van Gaal reported in Berlin, one year later, patients who had received daily doses of 20 mg of rimonabant had lost 6.6 kg on average; patients who took the lesser dose of 5 mg lost an average of 3.4 kg; patients who received the placebo lost only an average of 1.8 kg.

The group of patients with a daily dosage of 20 mg of rimonabant not only lost the most weight of all of the trial participants, but they lost it in the critical places of abdomen and waist. It is remarkable, according to Prof. Van Gaal, that in these patients, the risk factors for metabolic syndrome and cardiovascular diseases were reduced more than could be expected from mere loss of weight. He estimates that 50 percent of this effect is due to rimonabant. The reason: while patients who received the 5 mg dose of rimonabant clearly lost weight, their blood lipid levels were not as improved as in patients with the higher dose.

Few Side Effects
Exhibited side effects were nausea, diarrhea, and dizziness, but according to Professor Van Gaal, they were mild and transient. "According to current findings, rimonabant appears to be very promising, especially for the treatment of patients with abdominal obesity," Professor Van Gaal said in Berlin. The two-year study has now been concluded, and it is anticipated that the findings will be published next year.

Press and Public Affairs
Max Delbrück Center for Molecular Medicine(MDC) Berlin-Buch
Barbara Bachtler
Robert-Rössle-Str. 10
13125 Berlin
Phone: +49/30/9406-38 96
Fax.: +49/30/9406-38 33

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