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

Project description

Targeting metabolic drivers of cachexia in kidney disease

Patients suffering from chronic diseases often present with cachexia, a severe metabolic syndrome associated with involuntary weight loss and muscle wasting. Cachexia is characterised by an increase in inflammatory mediators and higher basal metabolic rate. It worsens the clinical outcome and quality of life of patients with chronic kidney disease, especially those on renal replacement therapy. With the support of the Marie Skłodowska-Curie Actions programme, the StopKidneyCachexia project aims to investigate the role of dysregulation in adipose tissue and liver in cachexia and reduce its devastating clinical burden. Researchers will dissect the mechanisms of systemic energy loss, identify early biomarkers and evaluate therapeutic targets in preclinical models.

Objective

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.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 242 260,56
Address
RUE DE TOLBIAC 101
75654 Paris
France
Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
No data