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Enhancing brown adipose tissue through NAD+ precursors: a new approach to treat cardiometabolic disease

Project description

Fat cells recruited to fight cardiovascular disease

Hundreds of years ago, scientists discovered brown adipose tissue (BAT) in marmots. Since then, interest in BAT has waxed and waned. It was found in other mammals and even in new-born and infant children, and a metabolic role for BAT has solidified. Loaded with mitochondria, these specialised fat cells generate body heat, no shivering required. Discovery in adults a decade ago and a demonstrated role in insulin sensitivity have generated renewed interest in BAT as a therapeutic route to treatments for potentially fatal cardiometabolic disease. The eBAT project is studying a potentially very potent activator of BAT in cell lines and animal models, and as a dietary supplement.

Objective

Cardiometabolic disease comprises a group of disorders including obesity, hypertension, dyslipidaemia, hypercholesterolaemia and glucose intolerance. These are the underlying cause of the majority of cardiovascular diseases, which represent the leading cause of morbidity and mortality in the Western World. The discovery of active brown adipose tissue (BAT) in adult humans in 2009 has increased the interest on the role of this tissue in the development of these disorders, and in the potential of its metabolic activation for their treatment. It has been demonstrated that BAT activation can be achieved by means of supplementation with NAD+ precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR). However, very little is known about how these compounds exert their effect on BAT and what the metabolic effects of their administration to this tissue are. This project proposes the use of an undescribed NAD+ precursor to induce BAT activation. I have already proved that this new compound is a more powerful NAD+-booster than NMN and NR. Thus, I hypothesize that it will be able to enhance BAT function more pronouncedly. By testing the effects of the supplementation of different cell lines and mouse models with this new compound, I aim to elucidate the molecular mechanisms underlying its NAD+-enhancing potential and the physiological changes that BAT undertakes upon its administration. Moreover, its encapsulation in nanoparticles for its oral administration through the diet will also be tested. This will be of outstanding relevance for its possible pharmacological use. The development of the research aims proposed in this project will shed light on the use of NAD+ precursors to activate BAT function, with the long-term ambition of establishing whether the use of these compounds is a suitable approach for the protection from cardiometabolic disease through the preservation of BAT phenotype.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

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Coordinator

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Net EU contribution
€ 175 572,48
Address
MEIBERGDREEF 15
1105AZ Amsterdam
Netherlands

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Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 175 572,48