Dr. Gema Frühbeck, manager of the laboratory of research Metabolic of the University Clinic of the University of Navarra, has published a commentary in the latest issue of the journal Nature. The work presents aquaporin as a new modulator of adipocyte biology. "It is a new concept of how glycerol permeability in fat cells is able to modulate adipocyte size and thus contributes to the development of obesity," explains Dr. Frühbeck.

Aquaporins are related to the transport of water across membranes, but only recently has their link to the control of body weight and adiposity been established. "There is a subfamily, the aquaglyceroporins, which in addition to water transport smaller solutes, such as glycerol. It has been seen that if the specific aquaporin of adipose tissue, aquaporin 7, is eliminated, the glycerol is not able to leave the fat cell and accumulates inside. In other words, adipocyte hypertrophy occurs, which, if maintained over time and occurs in many adipocytes simultaneously, leads to obesity". It has been proven that this aquaporin 7 also participates in insulinosensitivity. However, in humans, loss of function due to mutation of the gene has not been observed to be associated with development obesity or diabetes.

From now on, the researchers at laboratory of the Clinic have as goal to deepen in the pathophysiological status characteristic of human obesity and to evaluate the modulation of these channels as a possible therapeutic target.

Pioneer team

The Multidisciplinary Team for the diagnosis and treatment of obesity, directed by Dr. Salvador and integrated by specialists from Departments of Endocrinology, General Surgery, Neurophysiology, Cardiology, Pneumology, Anesthesiology, Biochemistry , etc., is a project started in 1999. Subsequently, the Clinic supported the creation of the laboratory of research Metabolic of the University of Navarra. According to Dr. Frühbeck, "it was a pioneering venture, which has allowed us to combine clinical attendance with basic research with an integrative and translational perspective".

The main area of study is the research of obesity and its comorbidities, from a clinical and molecular point of view. One of the lines of work is directed to the analysis of intracellular signaling. "Specifically, we focus on adipocyte and vascular smooth muscle cells and their link to hypertension and cardiovascular disease."

At partnership with the area of Cardiovascular Sciences at CIMA of the University of Navarra, the group coordinated by Dr. Frühbeck studies the involvement of leptin in blood pressure control. "We started by relating leptin and blood pressure, mainly through the release of nitric oxide."

The study of the functional relationship between leptin and nitric oxide forms the focus of other ongoing projects at laboratory of research Metabolic. "Leptin is mainly synthesized by the adipocyte, but there are also other tissues capable of synthesizing this cytokine. Moreover, functional leptin receptors are found in a multitude of organs, such as, for example, the liver. We hypothesize that leptin may play a beneficial role in liver regeneration, as it is involved in the intracellular signaling cascade involved in the regeneration of damaged tissue". Another fruitful line of research addresses changes in gastrointestinal hormones following bariatric surgery.

Factors involved

A few years ago it was believed that obesity had a primordial genetic component; that is, patients were obese because their genes conditioned them to be so. The laboratory of research Metabolic analyzes the profile of gene expression in this disease.

According to Dr. Frühbeck, "there are susceptibility genes that predispose to obesity. Some are more energy-sparing than others, while others favor energy release. However, within the same obesity phenotype, there are multiple causes. The current obesity epidemic is due more to sedentary lifestyles and changes in lifestyle habits than to a specific alteration Genetics . Undoubtedly, the development and perpetuation of obesity is due to the joint action of external environmental agents in combination with numerous genes".