Portal de investigación
Treatment with 1.25% cholesterol enriched diet produces severe fatty liver disease characterized by advanced fibrosis and inflammation and impaired autophagy in mice.
Fecha de publicación:
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Autores de INCLIVA
Participantes ajenos a INCLIVA
- Taberner-Cortés A
- Martín-Rodríguez RM
- Herrero-Cervera A
- Vinué Á
- Martín-Vañó S
Grupos y Plataformas de I+D+i
Abstract
Nonalcoholic fatty liver disease (NAFLD) is reaching pandemic proportions due to overnutrition. The understanding of advanced stages that recapitulate the human pathology is of great importance to get a better mechanistic insight. We hypothesized that feeding of WT (C57BL) mice with a diet containing a high content of fat (21%), sugar (41.5%) and 1.25% of cholesterol (called from now on high fat, sucrose and cholesterol diet, HFSCD) will reproduce the characteristics of disease severity. Analysis of 16 weeks HFSCD-fed mice demonstrated increased liver weight and plasmatic liver damage markers compared with control diet (CD)-fed mice. HFSCD-fed mice developed greater hepatic triglyceride, cholesterol and NEFA content, inflammation and NAFLD activity score (NAS) indicating an advanced disease. HFSCD-fed mice displayed augmented hepatic total CD3+ T and Th9 lymphocytes, as well as reduced Th2 lymphocytes and CD206 anti-inflammatory macrophages. Moreover, T cells and anti-inflammatory macrophages correlated positively and inversely, respectively, with intrahepatic cholesterol content. Consistently, circulating cytotoxic CD8+ T lymphocytes, Th1, and B cell levels were elevated in HFSCD-fed WT mice. Hepatic and adipose tissue expression analysis demonstrated changes in fibrotic and metabolic genes related with cholesterol, triglycerides, and fatty acid synthesis in HFSCD-fed WT. These mice also exhibited reduced antioxidant capacity and autophagy and elevated ERK signaling pathway activation and CHOP levels. Our results indicate that the feeding with a cholesterol-enriched diet in WT mice produces an advanced NAFLD stage with fibrosis, characterized by deficient autophagy and ER stress along with inflammasome activation partially via ERK pathway activation.
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 0955-2863, 1873-4847
- Tipo:
- Article
- Páginas:
- 109711-109711
- PubMed:
- 39111707
JOURNAL OF NUTRITIONAL BIOCHEMISTRY Elsevier BV
Citas Recibidas en Web of Science: 5
Documentos
- No hay documentos
Filiaciones
Keywords
- Cholesterol; Inflammation; Metabolism; NAFLD; Stress pathways
Financiación
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Cita
Taberner A,Aguilar M,Jiménez E,Hurtado G,Martín RM,Herrero A,Vinué Á,Martín S,Martínez S,González H. Treatment with 1.25% cholesterol enriched diet produces severe fatty liver disease characterized by advanced fibrosis and inflammation and impaired autophagy in mice. J Nutr Biochem. 2024. 134. p. 109711-109711. IF:4,900. (1).
Treatment with 1.25% cholesterol enriched diet produces severe fatty liver disease characterized by advanced fibrosis and inflammation and impaired autophagy in mice. Taberner A, Aguilar M, Jiménez E, Hurtado G, Martín RM, Herrero A, Vinué Á et al. JOURNAL OF NUTRITIONAL BIOCHEMISTRY. 2024 diciembre 01. 134109711-109711. DOI:10.1016/j.jnutbio.2024.109711. PMID:39111707.
