Psammomys obesus, a unique model of metabolic syndrome, inflammation and autophagy in the pathologic development of hepatic steatosis.
The aim of our transmission electron microscope study was to show, for the first time, the alteration of liver cells involved in the evolution of steatosis to steatohepatitis on a murine model of the diet-induced metabolic syndrome, Psammomys obesus. This pathologic evolution was induced by using the standard laboratory diet during 10 months, and analyzed with metabolic studies and the immunohistochemistry technique. Four months later, hepatocytes charged with lipid vacuoles were involved in autophagy. Furthermore, in the sinusoids, we observed Kupffer cells, neutrophils and macrophages. All those cells were associated with necrotic hepatocytes inducing hepatocellular necrosis. We also noticed a synthesis of extracellular matrix in excess, caused by proliferation and activation of hepatic stellate cells in necrotic areas. We observed as well a fragmentation of the endoplasmic reticulum, which formed isolated membranes (phagophores) surrounding mitochondria. The complex membrane-mitochondria formed like an autophagosome. Thus, a defect in autophagy favored the development and progression of steatohepatitis. In conclusion, our results suggest that P. obesus is very well adapted for experimental research, and could help improve the early therapeutic management of patients and the prevention of autophagic risks in the liver.
Laboratory of Biology and Physiology of Organisms/Molecular Modelling Endothelial Dysfunction and Diabetes, Faculty of Biological Sciences, University of Science and Technology Houari Boumediene (USTHB), P.O. Box 32, El Alia, Dar El Beida, 16111 Alger, Algeria. Electronic address: obeloui@yahoo.fr.
Ouahiba
O
Sihali-Beloui
Laboratory of Biology and Physiology of Organisms/Molecular Modelling Endothelial Dysfunction and Diabetes, Faculty of Biological Sciences, University of Science and Technology Houari Boumediene (USTHB), P.O. Box 32, El Alia, Dar El Beida, 16111 Alger, Algeria.
Salima
S
El-Aoufi
Laboratory of theoretical physical-chemistry and of Informatic Chemistry, Faculty of Chemistry, USTHB, El Alia, Dar El Beida, 16111 Alger, Algeria.
Boubekeur
B
Maouche
Institut Curie, Centre de Recherche, 91405 Orsay, France; Inserm, U1196, 91405 Orsay, France; CNRS, UMR9187, 91405 Orsay, France; Université Paris-Sud, Université Paris-Saclay, 91190 Saint-Auban, France.
Sergio
S
Marco
D000818:Animals; D001343:Autophagy; D001835:Body Weight; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology*; D005849:Gerbillinae / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology*; D009336:Necrosis; D009765:Obesity / Q000235:genetics / Q000473:pathology; D009929:Organ Size
Autophagie; Autophagy; Electron microscopy; Foie; Inflammation; Liver; Microscopie électronique; Psammomys obesus