Metabolic disorders induced the changes in the expressions of TNFα, E-cadherin and ultrastructural alteration of liver cells in a typical animal model of type 2 diabetes: Psammomys obesus

• Published in: Tissue & cell 2024-06, Vol.88, p.102396, Article 102396
• Main Authors: Sihali- Beloui, Ouahiba, Aroune, Djamila, Bellahreche, Zineb, Haniche, Nadia, Termeche, Amel, Semiane, Nesrine, Mallek, Aicha, Marco, Sergio
• Format: Article
• Language: English
• Subjects: Animals; Cadherins - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Disease Models, Animal; E-cadherin; Gerbillinae; High Calorie Diet (HCD); Liver - metabolism; Liver - pathology; Liver - ultrastructure; Liver disease; Male; Metabolic Diseases - metabolism; Metabolic Diseases - pathology; Metabolic disorders; Psammomys obesus; Tumor Necrosis Factor α (TNFα); Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0040-8166; 1532-3072; 1532-3072
• DOI: 10.1016/j.tice.2024.102396

By using a unique animal model of type 2 diabetes mellitus, Psammomys obesus induced by a high-calorie diet (HCD) for nine months, we showed for the first time, in the liver, the impact of inflammation on the remodeling of intercellular junction molecules E-cadherins during the progression of steatohepatitis. Under the effect of HCD, the expressions of immunohistochemical markers, Tumor Necrosis Factor alpha (TNFα) and E-cadherins were inversely correlated. Ultrastructural examination revealed the involvement of destabilization and loss of E-cadherins in the process of hepatic pathogenesis. This mechanical maintenance stress was favored by the recruitment of immune cells which contributed to the triggering and progression of fibrosis by the enlargement of the intercellular space and the invasion of collagen fibers. Furthermore to escape cell death, loss of E-cadherins played a major role in mediating fibrosis. Psammomys obesus is a promising model for experimental research, enabling the extrapolation of observed structural and functional alterations in humans, the objective to find new therapeutic targets. The physiological resemblance between Psammomys obesus and humans enhances the precision and relevance of biomedical research efforts. •The high-calorie diet induces in Psammomys obesus: recruitment and activation of immune cells and secretion of the pro-inflammatory cytokine Tumor Necrosis Factor alpha (TNFα).•Overexpression of TNFα causes liver cells damages and modifications in the expression of the adhesion molecule E-cadherin.•TNFα induces the dissociation, the loss of adherens junctions E-cadherin and participate of activation and proliferation of hepatic stellate cells.•The loss of E-cadherins damages the bile canaliculi by deposition of collagen.•Cellular alterations hepatic were lead to progression from Non-Alcoholic Fatty Liver.•Disease (NAFLD) to Non-Alcoholic Steatohepatitis (NASH) and Cirrhosis.