Guadalupe Sabio / Laura M. Lombardía. CNIO
The European Research Council has awarded one of its best endowed grants to Guadalupe Sabio, from the National Cancer Research Centre (CNIO) to search for a drug to protect the heart from harmful fat
The ADIPOhealth project a collaboration of four research groups from Spain, the United Kingdom, Denmark and the United States, coordinated by CNIO
“Fat communicates with other organs: understanding its language will allow us to anticipate the risks of obesity and develop new treatments to prevent and treat its associated diseases,” says Guadalupe Sabio
The results will help to understand the relationship between obesity and cancer, and to adapt tumour treatments in people with obesity
One fifth of the Spanish population is obese, a condition that increases the risk of cancer, cardiovascular diseases or diabetes. Until recently, it has been assumed that this risk is derived from the weight of their fat, “but that’s not the case,” says Guadalupe Sabio, head of the Metabolic Interactions Group at the National Cancer Research Centre (CNIO). “What matters is not the amount of fat but its quality and proper functioning. Fat is an organ whose cells have a function, and risk appears when they do not perform that function properly. However, we still don’t know how fat behaves and how that influences other organs and tissues.”
To further our knowledge in this area, the European Research Council (ERC) has just awarded a 10-million-euro ERC Synergy grant to the project ‘Deciphering the role of adipose tissue in heart health and disease: ADIPOhealth’. It is an international collaboration lasting six years, coordinated by Sabio. The CNIO group has been allocated around 3 million euros to decipher how fat communicates with the rest of our body.
It has been a very competitive call for funding. Of the 712 projects submitted, only 66 have received funding; they will be developed by research groups in 26 European countries and also the United States, as reported by the ERC.
Adipose tissue performs a key function in maintaining our health
Adipose tissue, or body fat, is an endocrine organ: its cells secrete molecules that travel through the blood and regulate the metabolism of other organs. When fat functions properly, these signals are beneficial; when it becomes dysfunctional, it can trigger diseases.
The project investigates the influence of adipose tissue on the heart, but the results will broaden our understanding of the general role of fat in the body, and particularly in diseases such as cancer.
The overweight and obese population is very diverse. Understanding the dysfunctionality of each person’s fat will show the likelihood of developing associated diseases, for example, who is more susceptible to having a heart attack or developing cancer. “This is also important for doctors, who currently lack tools to diagnose adipose tissue disease and, consequently, to know the real risks faced by a patient,” the researcher states.
Obesity increases the risk of heart failure, but tumour treatments also can. In fact, 60% of cancer treatment abandonment is due to heart problems. Understanding how fat cells control the heart would allow tumour treatments to be tailored for people who are overweight and obese.
The first objective of the ADIPOhealth project is to identify changes that occur in dysfunctional fat and how these changes are capable of altering the communication of fat cells, or adipocytes, with the heart. To do this, they will look for biomarkers: substances secreted by dysfunctional adipocytes. As these substances travel through the bloodstream, they could be used as therapeutic targets and very accessible treatments.
Thin people with dysfunctional fat
Biomarkers will allow us to detect which fat is healthy and which fat is not, in order to differentiate which overweight or obese individuals have a higher cardiovascular risk, ‘because their adipocytes are not functioning properly, and which ones maintain a low risk, because their adipocytes are functioning well,’ explains Sabio.
“There are also thin people who are unaware that they have dysfunctional adipocytes,” the metabolism expert stated, adding: “If your adipocytes are unable to store fat, that fat goes to the liver. You are a slim person, but you have a higher risk of having a fatty liver and, therefore, liver cancer.
To determine which biomarkers indicate the real risk for each person, Sabio’s team at CNIO will study animal models and human samples to ascertain why and to what extent the adipocyte is dysfunctional, and which substances it secretes when it is not functioning properly. The group headed up by Jesper Olsen, from the University of Copenhagen (Denmark), will be analysing proteins in different samples.
Ultimate goal: drugs in nanocapsules
Dale Abel from the University of California in Los Angeles (USA) will work with Sabio to determine which of these substances detected by their colleagues affect heart cells, which affect other tissues, and which serve as biomarkers. “In adipose tissue, we don’t have a marker that tells us: your adipose tissue is bad,” Sabio states.
The selected biomarkers will be compared in human samples. The results will define the key molecules to target in order to prevent the harmful effects of adipocyte dysfunction.
In a final phase, Sabio’s group will attempt to develop a drug for these target molecules, and then Mauro Giacca, from King’s College London (United Kingdom), will design nanoparticles that can be administered and reach the heart directly.
About ERC-Synergy grants
ERC-Synergy grants fund between two and four groups from different disciplines and countries to collectively address ambitious problems that could not be tackled individually, bringing together different skills and resources. This funding is part of the European Union’s Horizon Europe Research and Innovation Programme.
About the National Cancer Research Centre (CNIO)
The National Cancer Research Centre (CNIO) is a public research centre under the Department of Science, Innovation and Universities. It is the largest cancer research centre in Spain and one of the most important in Europe. It includes around five hundred scientists, along with support staff, who are working to improve the prevention, diagnosis and treatment of cancer.
About the European Research Council (ERC)
The ERC, created by the European Union in 2007, is Europe’s main organisation dedicated to funding excellence in research. It runs four grants programmes: Starting Grants, Consolidator Grants, Advanced Grants and Synergy Grants. An additional Proof of Concept programme helps beneficiaries bridge the gap between cutting-edge research and the early stages of commercialisation.