Keywords: leptin, organ failure, acute lung injury, acute kidney injury, biomarker Internship Duration: 30/11/-1 - 30/11/-1
Head of the hosting team: Alice HUERTAS
Address of the host laboratory: University Paris-Saclay INSERM UMR_S999 Team Microcirculation and acute organ failure University Paris-Saclay School of Medicine 63 Avenue Gabriel Peri 94270 Le Kremlin-Bicêtre France
Supervisor: Alice HUERTASE-mail: alice.huertas@inserm.fr Phone: + 33638833286
Leptin was first discovered as the satiety hormone, but it is well known now as a pleotropic hormone and a type I cytokine. Beyond food intake, leptin regulates a wide range of systemic physiological functions, in particular the immune system and inflammatory responses. Interestingly, leptin plays an important role in innate and adaptive immune responses in the lungs and contributes to pulmonary defense against injury. We recently showed that leptin is produced by the lungs and its receptor ObR is widely distributed in pulmonary cells, among other tissues, and contributes to the pathophysiology of chronic pulmonary diseases. Besides this knowledge, the role of leptin in acute settings, such as post-traumatic acute organ failure, and its signaling appears to be particularly controversial and a matter of debate as clinical data are lacking. Human studies are mostly in obese and/or diabetic patients, but the exact role of leptin, independently of body mass index, hyperleptinemia or metabolic disorders, is not yet understood. We hypothesize that leptin may represent a pathophysiological key player in post-traumatic acute organ failure, and in particular in acute kidney injury (AKI) as well as in acute lung injury (ALI), through its immunomodulatory properties and/or a useful biomarker. Therefore, our objectives are: 1. to better understand the role of leptin and its signaling pathway in acute organ failure 2. to investigate the organ-specificity of leptin pathophysiology (lung versus kidney) 3. to analyse the potential role of leptin as a disease severity biomarker in post-traumatic acute organ failure This project is a translational study, combining human data from the Intensive Care Unit of Bicêtre hospital and in vivo rodent models of severe trauma.
flow cytometry ELISA in vivo rodent models
Jutant EM, et al. The Thousand Faces of Leptin in the Lung. Chest. 2021;159(1):239-248 ` Huertas A, et al. Leptin and Treg lymphocytes in idiopathic PAH. Eur Respir J. 2012 ;40(4):895-904 Huertas A, et al. Leptin signalling system as a target for pulmonary arterial hypertension therapy. Eur Respir J. 2015;45(4):1066-80 Harrois A, et al. Acute kidney injury is associated with a decrease in cortical renal perfusion during septic shock. Crit Care. 2018; 22:161 Harrois A, et al. Prevalence and risk factors for acute kidney injury among trauma patients: a multicenter cohort study. Crit Care. 2018; 22:344
