Limiter l'activation des macrophages pour atténuer les maladies cardio-métaboliques // Limiting macrophage activation to mitigate cardio-metabolic diseases

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The prevalence of metabolic diseases, such as obesity, has increased at an exponential rate in recent decades. Obesity-related comorbidities include diabetes, hypertension, dyslipidemia, cardiovascular diseases, and fatty liver disease (MAFLD). MAFLD, particularly at the stage of steatohepatitis with inflammation and fibrosis (MASH), is also an independent risk factor for the development of cardiovascular diseases, especially atherosclerosis. The immune system is increasingly recognized as a key player in maintaining metabolic homeostasis. In particular, macrophages now hold a significant role in the emerging fields of immunometabolism and metaflammation. Present in all tissues of the body, these cells can be established as early as the embryonic stage (resident macrophages), while others are specifically recruited under pathological conditions. Although macrophages exhibit a broad spectrum of activation depending on the tissue and pathophysiological context, certain common denominators are found in cardiometabolic disorders. For example, lipid-associated foam cell macrophages, also known as LAMs, have been identified in both humans and murine models within atherosclerotic plaques, obese adipose tissue (AT), and MASH.

Current literature and our preliminary data suggest that one specific transcription factor (TF) not only drives the pro-inflammatory and pro-fibrotic activation of macrophages but also regulates their lipid handling capacity. Using murine models, our objectives are to assess whether reprogramming macrophages by inactivating this TF can mitigate the chronic inflammatory and fibrotic response observed in metabolic tissues (adipose tissue, liver) and atherosclerotic lesions and, more broadly, reduce cardiometabolic damage. This work could therefore indicate whether this TF represents a potential therapeutic target for treating these multi-organ pathologies.
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Début de la thèse : 01/10/2025

Public funding alone (i.e. government, region, European, international organization research grant)

Concours pour un contrat doctoral

Sorbonne Université SIS (Sciences, Ingénierie, Santé)

394 Physiologie, physiopathologie et thérapeutique

Candidate pressentie : Fanny Xie fanny.xie.1@etu.sorbonne-universite.fr fannyx2810@outlook.fr
Candidate pressentie : Fanny Xie fanny.xie.1@etu.sorbonne-universite.fr fannyx2810@outlook.fr