New insights into therapeutic strategies for obesity-induced chronic kidney disease: is there a central role for AMP-activated protein kinase?

Promoters

Prof. Nathalie CARON, UNamur, Molecular Physiology Research Unit (URPhyM)

Prof. Anne-Emilie DECLEVES, UMons, Laboratory of Metabolic and Molecular Biochemistry

Jury

Président du Jury : Prof. J-M. COLET (UMONS)

Président du Jury : Prof. C. NICAISE (UNamur)

Secrétaire du Jury : Dr. A. TASSIN

Membres : Dr. B. VIOLLET; Dr. F. JOURET; Prof. T. ARNOULD

Summary

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.