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

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

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.
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Coordinator

Academisch Medisch Centrum bij de Universiteit van Amsterdam

Address

Meibergdreef 9
1105az Amsterdam

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 175 572,48

Project information

Grant agreement ID: 840110

Status

Ongoing project

  • Start date

    1 June 2019

  • End date

    31 May 2021

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 175 572,48

  • EU contribution

    € 175 572,48

Coordinated by:

Academisch Medisch Centrum bij de Universiteit van Amsterdam

Netherlands