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Contribution of adipose tissue and liver to cachexia associated with chronic kidney disease

Descrizione del progetto

Prendere di mira i fattori metabolici che determinano la cachessia nelle malattie renali

I pazienti affetti da malattie croniche sono spesso affetti da cachessia, una grave sindrome metabolica associata a perdita di peso involontaria e deperimento muscolare che viene caratterizzata da un aumento dei mediatori infiammatori e da un tasso metabolico basale più elevato. Questo disturbo peggiora l’esito clinico e la qualità di vita dei pazienti che soffrono di malattia renale cronica, e soprattutto di quelli sottoposti a terapia sostitutiva renale. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto StopKidneyCachexia si propone di studiare il ruolo svolto dalla disregolazione del tessuto adiposo e del fegato nella cachessia e di ridurre il suo devastante carico clinico. I ricercatori analizzeranno i meccanismi relativi alla perdita di energia sistemica, identificheranno i biomarcatori precoci e valuteranno gli obiettivi terapeutici in modelli preclinici.

Obiettivo

Cachexia is a life-threatening wasting syndrome, defined by an involuntary loss of body weight, that affects a large proportion of patients with advanced chronic diseases. Kidney diseases affect > 850 million people worldwide and represent the 10th leading cause of death. In this context, cachexia associated with chronic kidney diseases (KCx) is a huge burden in end-stage patients with kidney replacement therapies. Patients with KCx experience frailty, which worsens their quality of life (impacting their social- and professional life), hospitalization and mortality rates. So far, most research efforts have tried to identify primary pro-cachectic factors contributing to muscle wasting, but this was unfruitful in terms of therapeutics. Here, we are proposing a translational and interdisciplinary project that will focus on novel tissues (i.e adipose tissue and liver) with great relevance in the control of systemic energy metabolism. Preliminary data obtained in collaboration with the host laboratory have shown that these two tissues undergo a strong remodeling of their glucose and lipid metabolism, which could contribute to energy loss and body wasting. The main objectives of the project will be: 1) to understand the mechanisms by which altered metabolic pathways contribute to wasting in fat, liver and muscle cells; 2) to assess the biomarker potential of products of these metabolic pathways for early diagnosis of patients with KCx; and 3) to assess the therapeutic potential of targeting these metabolic pathways in mouse models of KCx. With this project, we will develop a novel research axis combining my expertise in the field of cachexia and metabolism to the expertise of the host in the field of kidney diseases. The project will be supported by highly relevant in vitro and in vivo models, access to patients’ samples, and innovative techniques. This fellowship will allow to develop my independency and to get a competitive research profile to pursue an academic career.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(si apre in una nuova finestra) HORIZON-MSCA-2024-PF-01

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Coordinatore

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Contributo netto dell'UE
€ 242 260,56
Indirizzo
RUE DE TOLBIAC 101
75654 Paris
Francia
Regione
Ile-de-France Ile-de-France Paris
Tipo di attività
Research Organisations
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Costo totale
Nessun dato