Blood vessels regulate obesity through a molecular communication

The abundance and function of blood vessels in adipose tissue conditions the development of obesity. This is the surprising conclusion reached by the study published in Nature Metabolism.

Obesity is a multifactorial epidemic disease closely related to the development of multiple pathologies, originated by the exacerbated expansion of adipose tissue. The development of prevention and treatment strategies for this disease is, therefore, an urgent biomedical need. Adipose tissue has important blood supply requirements, and the contribution of vessels to the development of obesity had not been clarified until now.

In order to clarify the contribution of blood vessels to the development of obesity, the authors studied a mouse model with increased vascular functionality, and observed that the animals were resistant to the development of obesity. "At that moment we knew that the vessels were instructing the body to control the management of fat," says the senior author. From this point on, the research team focused its efforts on identifying the mechanism in the vessel’s crosstalk with the adipose tissue. "It has been a process in which we have had to turn to cancer research to understand obesity," says the author.

The leaders of this research integrated international experts in different disciplines into the project to provide a comprehensive response to the phenomenon they just described. Years of research led to the conclusion that blood vessels use a language of communication based on small molecules or "metabolites" to instruct adipose tissue.

The adipocytes, in response to the message from the vessels, release fat, which the vessels capture as food to proliferate. The author continues "it is paradoxical that the mechanism by which the vessels produce these metabolites is identical to the one we recently described in the context of prostate cancer." And the author adds "while the vessels activate this process during a controlled increase in proliferation, the tumor cells do so in an uncontrolled and aberrant way".

The authors show that local production of polyamines in endothelial cells stimulates adipocyte lipolysis and regulates WAT homeostasis in mice. The authors promote enhanced cell-autonomous angiogenesis by deleting Pten in the murine endothelium. Endothelial Pten loss lead to a WAT-selective phenotype, characterized by reduced body weight and adiposity in pathophysiological conditions. This phenotype stems from enhanced fatty acid β-oxidation in ECs concomitant with a paracrine lipolytic action on adipocytes, accounting for reduced adiposity. Combined analysis of murine models, isolated ECs and human specimens reveals that WAT lipolysis is mediated by mTORC1-dependent production of polyamines by endothelial cells.

This study sheds light on the importance of blood vessels in regulating health and disease in our body. "Vessels have historically been considered inert blood transport tubes, but we are discovering that they perceive alterations in our body and respond by regulating and organizing the function of multiple tissues." The author concludes “the fact that the vessels respond differently in each organ suggests that we are facing a tissue that is specialized throughout our body, and this opens up exciting opportunities to improve human health through the regulation of blood vessels".