The influence of different fat sources on steatohepatitis and fibrosis development in the Western diet mouse model of non-alcoholic steatohepatitis (NASH)
Non-alcoholic steatohepatitis (NASH) is the leading cause of chronic liver injury and ranks as the third most common reason for liver transplants in Western countries. However, the influence of different fat sources in Western diets (WD) on NASH development remains unclear. This study investigates t...
| Autores: | , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad del País Vasco |
| Repositorio: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/71979 |
| Acceso en línea: | http://hdl.handle.net/10810/71979 |
| Access Level: | acceso abierto |
| Palabra clave: | non-alcoholic steatohepatitis Western diet fatty liver fibrosis animal model and liver injury |
| Sumario: | Non-alcoholic steatohepatitis (NASH) is the leading cause of chronic liver injury and ranks as the third most common reason for liver transplants in Western countries. However, the influence of different fat sources in Western diets (WD) on NASH development remains unclear. This study investigates the impact of non-trans fat (NTF) and corn oil (Corn) as dietary fat sources on the progression of NASH in a WD mouse model. C57BL/6J wildtype (WT) mice were fed a "standard" WD (WD-Std), WD enriched with NTF (WD-NTF), or WD enriched with Corn (WD-Corn) for 24 weeks. Mice treated with WD-NTF exhibited distinct features of metabolic syndrome compared to those on WD-Std and WD-Corn, including worsened insulin resistance and significantly elevated serum ALT, cholesterol, and triglyceride (TG) levels. In contrast, mice fed WD-Corn demonstrated a tendency toward reduced disease progression, as evidenced by milder changes in these parameters. After 24 weeks, all diets—WD-NTF, WD-Std, and WD-Corn—led to comparable initiation of steatohepatitis, characterized by histomorphological changes and immune cell infiltration. Notably, immune cell infiltration was associated with a significant increase in mRNA expression of pro-inflammatory cytokines IL-6 and TNF-α, which was most pronounced in the WD-NTF group. Interestingly, the fat source did not influence the composition of accumulated fat in liver tissue, as assessed by matrix-assisted laser desorption/ionization mass spectrometry imaging of various lipid classes. However, the choice of dietary fat did affect fibrosis development. WD-NTF resulted in substantial collagen accumulation, indicating pronounced fibrosis, while WD-Corn appeared to protect against extracellular matrix deposition. An unexpected finding was the effect of WD-Corn on epididymal white adipose tissue (eWAT). WD-Corn induced significant histomorphological changes and severe extracellular matrix accumulation in eWAT, alterations not observed in mice fed WD-Std or WD-NTF. In summary, different fat sources in WD significantly influence the development of steatohepatitis and its associated features in WT mice after 24 weeks. Both WD-NTF and WD-Corn serve as viable alternatives to WD-Std in modeling steatohepatitis. However, WD-Corn uniquely induces profound changes in eWAT morphology, highlighting its distinct effects on adipose tissue. |
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