Fat: An active player in the regulation of many processes in health and disease

Basic Science Track: Links between obesity and coronary artery disease; The adipocyte as an endocrine organ 155001.

Vienna, Austria, 4 September 2007:

Why should we be interested in doing obesity-related research? Emphasis is put on this type of research simply because of the fact that the epidemiological data and predictions are alarming. Worldwide it is estimated that one person in every eight is overweight and more than 300 millions are obese. For a definition of overweight and obesity see Table 1 at the end of the press release.

Data collected by the International Obesity TaskForce (IOTF; see also http://www.iotf.org/database/index.asp) and by the WHO (see also: http://www.who.int/bmi/index.jsp) suggests that more than half of the population in the European Union (EU) is overweight. According to the IOTF in Austria one person in three is overweight and one person in five is obese. It is predicted that the incidence of obesity will double in the next four decades in Europe. Adding to the alarming situation is the observation that in all countries where surveys have been performed, the numbers of overweight and obese children have increased dramatically. It is predicted that in the EU 26 million schoolchildren will be overweight by the year 2010 of which 6 million will be obese. By that time these numbers will grow annually by 1.3 million and 0.3 million, respectively.

Obesity does not only mean a loss of quality of life for the affected person but also increases the risk of suffering from other diseases such as cardiovascular disease, certain cancers, diabetes, liver malfunction and orthopedic dysfunction. Our research focus is on studying the link between obesity and cardiovascular disease in general and atherosclerosis in particular. It is well known now, that obese individuals are at higher risk of developing cardiovascular diseases and several studies suggest obesity as an independent risk factor.

Adipose tissue is no longer seen merely as a mostly passive energy storage organ but is now also considered to be an active endocrine tissue that by producing a variety of cytokines, hormones and other proteins impacts on a multitude of physiological and pathophysiological processes in the human body. The adipocyte, whose size and numbers are increased in obesity, is the cellular factory that produces these proteins termed adipokines. We have cultured adipocytes from human adipose tissue and used them as a model to study effects of inflammatory mediators on the production of various adipokines by these cells.

The rationale behind this approach is based on the notion that obesity is associated with a state of chronic inflammation, which is in contrast to acute inflammation, which is in most cases a life-saving defence reaction of the body against infection that leads to tissue damage and destruction. Such tissue damage is thought to be the initiating event in the development of atherosclerotic blood vessels.

By using this approach we were the first to show that certain inflammatory mediators increase the production of two key adipokines, namely plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) by adipocytes. PAI-1 is a prothrombotic protein that promotes the development of blood clots. The development of such clots in atherosclerotic blood vessels is a key event in cardiovascular diseases such as myocardial infarction. Thus we believe that through these findings we have established a link between inflammation, adipose tissue and the development of cardiovascular disease.

VEGF is a protein, which induces the growth of new blood vessels. It is believed that adipose tissue, when it increases in mass, needs additional blood vessels to secure its supply with nutrients and oxygen. In fact, in mice it has been shown that blockade of VEGF leads to a decrease in adipose tissue mass in these animals. We were able to show in mice, for the first time, that inflammatory mediators injected into these animals led to increased blood vessel growth in adipose tissue. Such increase in blood vessel density in adipose tissue would then in turn result in better supply with oxygen and nutrients and could ultimately lead to growth of adipose tissue.

In conclusion we suggest that knowledge of regulatory mechanisms, which impact on the production of adipokines and on adipose tissue development and growth is instrumental to develop and improve strategies for combating not only obesity but also cardiovascular disease.