H2020Индивидуална стипендия2019–2021

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-06-01 → 2021-05-31
Финансиране от ЕС: 175 572 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Новото вещество NMNH се изследва като средство за повишаване на нивата на NAD+ и активиране на кафяната мастна тъкан. Това може да помогне при борбата с кардиометаболитни заболявания като затлъстяването, хипертонията и диабета.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

Cardiometabolic disease comprises a group of disorders including obesity, hypertension, dyslipidemia, hypercholesterolemia and glucose intolerance. These are the underlying cause of the majority of cardiovascular diseases, which represent the leading cause of 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, the promising results obtained in preclinical studies have been difficult to translate to humans, where NMN and NR have only shown very mild effects. This lack of beneficial effects in humans could be due to the limitations that these molecules have, including maximal NAD+-enhancing effects of 2-fold, the need of high doses, or their rapid degradation in plasma to nicotinamide (NAM). Therefore, we are now in need for more potent NAD+ boosting molecules. This MSCA IF project (eBAT) is focused on the use of a previously undescribed NAD+ precursor, namely reduced nicotinamide mononucleotide (NMNH), as a powerful NAD+ enhancer in vitro and in vivo, with the long-term goal of inducing BAT activation and fight metabolic disease in humans. During the course of the eBAT project, I have identified NMNH as an NAD+ precursor for the first time, studied its impact on the cellular NAD+ metabolome thanks to the development of a dedicated mass spec method, and elucidated the molecular mechanisms behind this molecule’s great potential to boost NAD+ levels. Moreover, I have conducted a mouse study in which I have identified NMNH as an active molecule also in vivo, with greater NAD+-enhancing effects in every tissue tested, including BAT, than its oxidized counterpart NMN. The results obtained in this project are of outstanding relevance for the future pharmacological use of NMNH as an NAD+ enhancer in mouse models of metabolic disease and, in the long-term, for its clinical application.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM · AmsterdamКоординаторНидерландия