Autophagy; Energy mobilization; LC3II; Liver cytolysis; Liver injury model; Nutritional status; Organ protection
Abstract :
[en] OBJECTIVE: Dietary and energetic restrictions are endowed with protection against experimental injuries. However, a drop in cell energetic status under a critical threshold may prevent protection, as previously observed for livers isolated from rat donors undergoing 18-h fasting versus feeding. The aim of this study was to further explore, in the latter model, links between nutritional status, energy availability, and protection through lengthening of rat fasting to 24 h and withdrawal of energy sources from perfusions. METHODS: Energy-free perfused ex vivo livers from fed, 18-h-fasted, and 24-h-fasted rats were studied during 135 min for cytolysis (potassium, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase releases in perfusates), cell deaths (activated caspase-3 [apoptosis], LC3 II/actin and p62/actin ratios [autophagy]), glycogen stores, glucose, and lactate production. RESULTS: Cytolysis was significantly increased by 18-h and 24-h fasting versus feeding but unexpectedly the increase was less for 24-h fasting than it was for 18-h fasting. Apoptotic marker caspase 3 significantly increased under fed and 18-h fasting but not 24-h fasting conditions. Autophagic marker LC3 II/actin significantly increased during perfusion in the 24-h fasted group but neither fed nor 18-h fasted groups. Autophagic induction also was supported by a drop in the p62/actin ratio. Under perfusion with 3-methyladenine, a standard autophagy inhibitor, protection and enhanced autophagy provided by 24-h but not 18-h fasting were lost without affecting apoptosis. CONCLUSIONS: Liver protections are obviously influenced by nutritional status in a way that is parallel to hepatic energy mobilization capacities (glycogen plus autophagy) with a decreased order of protection: Fed >24-h fasted >18-h fasted >24-h fasted+3-methyladenine livers. By showing that autophagy induction limits starvation-induced cytolysis, the present work supports the emerging view that autophagy inducers might improve health benefits of diet restriction.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Papegay, Berengere; Centre Hospitalier Universitaire de Charleroi
Nuyens, Vincent; Centre Hospitalier Universitaire de Charleroi
Albert, Adelin ; Université de Liège - ULiège > Département des sciences de la santé publique > Département des sciences de la santé publique
Cherkaoui-Malki, Mustapha; Université de Bourgogne-Franche Comté
Leo, Oberdan; Université Libre de Bruxelles - ULB
Kruys, Veronique; Université Libre de Bruxelles - ULB
Boogaerts, Jean G.; Centre Hospitalier Universitaire de Charleroi
Vamecq, Joseph; Institut National de la Santé et de la Recherche Médicale - INSERM > Biochemistry and Molecular Biology Laboratory
Language :
English
Title :
Protection in a model of liver injury is parallel to energy mobilization capacity under distinct nutritional status.
Publication date :
2019
Journal title :
Nutrition
ISSN :
0899-9007
Volume :
67-68
Pages :
110517
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2019 Elsevier Inc. All rights reserved.
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