New insights into therapeutic strategies for obesity-induced chronic kidney disease

: Is there a central role for AMP-activated protein kinase?

Abstract

Since the last decades, obesity has become epidemic worldwide largely due to the combination of our sedentary lifestyle, associated with a high caloric intake and the lack of physical activity. Accumulating studies have reported that obesity is a significant risk factor for chronic kidney disease (CKD) and the second most highly prognostic factor to predict end-stage renal disease. Evidence of a dysregulation of AMP-activated protein kinase (AMPK) activity in proximal tubular cells in obesity condition has been particularly demonstrated. AMPK is a central mediator of energy homeostasis responsive to nutritional and metabolic stresses such as obesity but is also a key regulator of autophagy and mitochondrial homeostasis. Despite considerable efforts in the development of new therapeutic strategies for obesity-related diseases, there is still a lack of effective treatment without strong side effects, particularly for obesity-induced CKD. In this thesis, the effects of exercise training intervention in a mice model presenting obesity-induced CKD was investigated. We particularly highlighted potential biomarkers that could be targeted with a dietary compound as an exercise mimetic to treat or prevent obesity-induced CKD. Furthermore, the central role of AMPK pathway regulation in this pathological context and in the responsiveness of each treatment was particularly evaluated.

Date of Award	2022
Original language	English
Awarding Institution	University of Namur Université de Mons (UMons)
Sponsors	University of Namur & Université de Mons (UMons)
Supervisor	Anne-Emilie DECLEVES (Supervisor), Nathalie Caron (Co-Supervisor), Jean-Marie Colet (President), Alexandra Tassin (Jury), Thierry Arnould (Jury), Charles Nicaise (Jury), François Jouret (Jury) & Benoit Viollet (Jury)