Aquaporin related to obesity

Dec 21 2005

Dr. Gema Fruhbeck, director of the Metabolic Research Laboratory of the University Hospital of the University of Navarra, has published a commentary in the latest issue of Nature. The article presents aquaporin as a new modulator of the biology of the adipocyte. It is a new concept concerning how the permeability of glycerol in fat cells is able to modulate the size of the adipocyte and, as a result, can contribute to the development of obesity.

Aquaporins are related to the transport of water through cell membranes, but only recently has they been linked to weight control and adiposity. There is a subfamily, the aquaglyceroporins, which transport water as well as smaller solutes, such as glycerol. It has been shown that if one eliminates the specific aquaporin of the adipose tissue, aquaporin-7, glycerol is no longer able to leave the fat cell and instead accumulates in the cell interior. That is to say, it produces a hypertrophy of the adipocyte, which if maintained over time, and in many adipocytes simultaneously, results in obesity. It has been shown that this aquaporin-7 also participates in insulin sensitivity. Nevertheless, in humans the loss of this function as a result of gene mutation has not been observed to be associated with the development of obesity or diabetes.

From now on the researchers from this laboratory of the Hospital will have as their objective the deepening of their understanding of the physico-pathologic situation common to human obesity and the evaluation of these channels as a possible means for therapeutic treatment.

Pioneering team

The Multidisciplinary Team of diagnosis and treatment of obesity is a project begun in 1999. Later, the Hospital aided in the creation of the Metabolic Research Laboratory of the University of Navarra.

The principal area of study is research of obesity and related morbidities, from a clinical and molecular point of view. One of the lines of research is directed towards the analysis of intracellular signaling. In particular, we are focusing on the adipocyte and smooth vascular muscle cells, and their linkage with hypertension and cardiovascular diseases.

In collaboration with the area of Cardiovascular Sciences of the CIMA of the University of Navarra, the group which Dr. Fruhbeck coordinates studies the participation of leptin in the control of arterial pressure. We are beginning to relate leptin and arterial pressure, especially by means of the liberation of nitric oxide.

The study of the functional relationship between leptin and nitric oxide constitute the axis of other projects in progress at the Metabolic Research Laboratory. Leptin is synthesized primarily by the adipocyte, but there also exist other tissues capable of synthesizing this cytokyne. In addition, the functional receptors of leptin are found in a great quantity of organs, such as, for instance, the liver. Our hypothesis is that leptin can play a beneficial role in liver regeneration, since it is implicated in the intracellular signal cascade typical of the regeneration of damaged tissue.

Implicated factors

It has been theorized for years that obesity has a primordial genetic component: that is, patients tend to be obese because their genes condition them in that direction. The Metabolic Research Laboratory analyses the profile of gene expression in this disease.

There are genes of susceptibility which predispose a person to suffering obesity. Some people are greater savers of energy than others, while other people tend to favor the liberation of energy. Nevertheless, in a single phenotype of obesity there are multiple causes. The current epidemic of obesity is mostly due to sedentary living habits and the changes of living habits, rather than to any particular genetic alteration. Without a doubt, the development and perpetuation of obesity is due to the joint action of external environmental factors in combination with numerous genes.

The Nutrition Society's "Sir David Cuthbertson" medal was awarded to Dr. Gema Frühbeck for her contribution in the investigation of obesity.