Western Diet-Fed ApoE Knockout Male Mice as an Experimental Model of Non-Alcoholic Steatohepatitis

Autor(es)

Camargo, Felipe N. ; Matos, Sandro L. ; Araujo, Layanne C. C. ; Carvalho, Carla R. O. ; Amaral, Andressa G. ; Camporez, Joao Paulo

• Tipo de documento: Artigo Científico
• Fonte: CURRENT ISSUES IN MOLECULAR BIOLOGY; v. 44, n. 10, p. 12-pg., 2022-10-01.

Resumo

One of the consequences of the Western lifestyle and high-fat diet is non-alcoholic fatty liver disease (NAFLD) and its aggressive form, non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma (HCC) and is rapidly becoming the leading cause of end-stage liver disease or liver transplantation. Currently, rodent NASH models lack significant aspects of the full NASH spectrum, representing a major problem for NASH research. Therefore, this work aimed to characterize a fast rodent model with all characteristic features of NASH. Eight-week-old male ApoE KO mice were fed with Western diet (WD), high fatty diet (HFD) or normal chow (Chow) for 7 weeks. Whole-body fat was increased by similar to 2 times in WD mice and HFD mice and was associated with increased glucose intolerance, hepatic triglycerides, and plasma ALT and plasma AST compared with Chow mice. WD mice also showed increased galectin-3 expression compared with Chow or HFD mice and increased plasma cholesterol compared with Chow mice. WD and HFD displayed increased hepatic fibrosis and increased F4/80 expression. WD mice also displayed increased levels of plasma MCP-1. Hepatic inflammatory markers were evaluated, and WD mice showed increased levels of TNF-alpha, MCP-1, IL-6 and IFN-gamma. Taken together, these data demonstrated that the ApoE KO mouse fed with WD is a great model for NASH research, once it presents the fundamental parameters of the disease, including hepatic steatosis, fibrosis, inflammation, and metabolic syndrome. (AU)

• Processo FAPESP: 18/04956-5 - Impacto do receptor de estrogênio alpha na Doença Hepática Gordurosa não Alcoólica e metabolismo energético do fígado
• Beneficiário: João Paulo Gabriel Camporez
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 19/18965-9 - Efeito do aumento da expressão por vírus adeno associado do receptor de estrogênio alfa sobre o metabolismo hepático
• Beneficiário: Felipe Nunes de Camargo
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 20/09094-1 - Impacto da inibição de galectina-3 sobre a resistência hepática à insulina e metabolismo energético na Esteato-Hepatite Não Alcoólica
• Beneficiário: Layanne Cabral da Cunha Araujo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado