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2021-05-14 - Colloque/Présentation - communication orale - Anglais - page(s)

Juszczak Florian , Decarnoncle Morgane, Tassin Alexandra , Decleves Anne-Emilie , "New insights into therapeutic strategies for obesity-induced chronic kidney disease: is there a role for AMPK" in International Webinar on Nephrology, Urology and Kidney Failure, Webinar (Online Meeting), 2021

  • Codes CREF : Pathologies particulières (DI3370)
  • Unités de recherche UMONS : Biochimie métabolique et moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Mind & Health (CREMH)

Abstract(s) :

(Anglais) Chronic Kidney Disease (CKD) is associated with highly prevalent physiological and metabolic disturbances such as hypertension, obesity, insulin resistance, cardiovascular disease, and aging, which are also risk factors for both CKD pathogenesis and progression. AMP-activated protein kinase (AMPK) is an important energy sensor that plays a critical role in regulating glucose and lipid metabolism, in playing a key role in mitochondrial homeostasis and autophagy in mammalian cells. We and others have demonstrated AMPK dysregulation as a main driver of obesity-induced CKD while traditional pharmacological AMPK activation was constantly associated to beneficial outcomes. However, since these traditional AMPK activators present a limited clinical use, particularly for kidney disease, we recently investigated the effects of behavioral therapeutic strategy to restore AMPK activity in kidney. Therefore, we tested a delayed endurance exercise training (EET) in high-fat diet-fed mice presenting CKD. We better described the restorative effects of EET on obesity-induced impairments such as glucose tolerance, insulin resistance or dyslipidemia and hepatic steatosis. These data were concordant with clinical studies in obese patients demonstrating the translational relevance of our experimental model. We further demonstrated for the very first time the beneficial effects of a delayed exercise on inflammation, fibrosis, and oxidative stress intra-renal environment. Particularly, ectopic lipid accumulation in proximal tubule was decreased with exercise associated to an improved AMPK pathway, as previously demonstrated with AICAR treatment in the same experimental model. The regulation of signaling pathways by AMPK in response to a high fat diet and/or exercise requires further investigation and mechanistic studies to further confirm the role of AMPK activity in obesity-induced CKD and in treatment response.

(Anglais) Chronic Kidney Disease (CKD) is associated with highly prevalent physiological and metabolic disturbances such as hypertension, obesity, insulin resistance, cardiovascular disease, and aging, which are also risk factors for both CKD pathogenesis and progression. AMP-activated protein kinase (AMPK) is an important energy sensor that plays a critical role in regulating glucose and lipid metabolism, in playing a key role in mitochondrial homeostasis and autophagy in mammalian cells. We and others have demonstrated AMPK dysregulation as a main driver of obesity-induced CKD while traditional pharmacological AMPK activation was constantly associated to beneficial outcomes. However, since these traditional AMPK activators present a limited clinical use, particularly for kidney disease, we recently investigated the effects of behavioral therapeutic strategy to restore AMPK activity in kidney. Therefore, we tested a delayed endurance exercise training (EET) in high-fat diet-fed mice presenting CKD. We better described the restorative effects of EET on obesity-induced impairments such as glucose tolerance, insulin resistance or dyslipidemia and hepatic steatosis. These data were concordant with clinical studies in obese patients demonstrating the translational relevance of our experimental model. We further demonstrated for the very first time the beneficial effects of a delayed exercise on inflammation, fibrosis, and oxidative stress intra-renal environment. Particularly, ectopic lipid accumulation in proximal tubule was decreased with exercise associated to an improved AMPK pathway, as previously demonstrated with AICAR treatment in the same experimental model. The regulation of signaling pathways by AMPK in response to a high fat diet and/or exercise requires further investigation and mechanistic studies to further confirm the role of AMPK activity in obesity-induced CKD and in treatment response.