In this study, mouse models were generated in which the mitochondrial function of the endothelial cells is specifically modified. This manipulation causes moderate mitochondrial stress that activates protective mechanisms, improves the ability to oxidise fats, and strengthens antioxidant defences. As a result, the animals presented a thinner phenotype, more efficient use of glucose, marked protection against obesity induced by high-fat diets and, in addition, the preservation of the motor and cognitive functions associated with quality of life during ageing.
According to Marc Claret, head of the research group and one of the project leaders: “We have discovered that the endothelium is much more than a passing layer. A modification in its mitochondria is sufficient to trigger responses with beneficial effects for the whole body. This forces us to rethink how we understand the regulation of metabolism and opens up a completely new pathway in research into metabolic diseases.”
Until now, the majority of studies on obesity and diabetes had focused on organs such as the liver, muscle, adipose tissue, or the brain. This study positions endothelial cells as a key actor, capable of perceiving changes in the body’s energy status and activating responses that spread throughout the organism. Among these responses is an increase in certain molecules with systemic effects, which contribute to the benefits observed with regard to weight, metabolism, and resistance to ageing.
Claret also highlights the translational significance of the discovery, stating that: “If, in the future, we are able to modulate these adaptive responses of the endothelium safely, we could develop completely new strategies to prevent or treat obesity, type 2 diabetes, and age-related deterioration”. This view opens the door to considering the endothelium as a possible therapeutic target in disorders that have been difficult to address until now.
The study is the result of national and international collaboration between several research centres, such as the Josep Carreras Leukaemia Research Institute and ETH Zurich. The project has enjoyed the financial support of multiple national and international agencies, prominently including the European Research Council (ERC), the Spanish Ministry of Science and Innovation, the Generalitat de Catalunya, the "la Caixa" Foundation, and the BBVA Foundation.
Study of reference
Deletion of Mfn2 in endothelial cells triggers a mitohormetic response that improves systemic metabolism and healthspan in mice. Chivite, Iñigo et al. Cell Metabolism, Volume 0, Issue 0
