ABSTRACT
Background: Non-alcoholic fatty liver disease (NAFLD), a condition that leads to fibrosis, is caused by intake of very high-fat diets (HFDs). However, while the negative impact on the liver of these diets has been an issue of interest, systematic research on the effect of HFDs are lacking. Objective: To characterize the overall impact of HFDs on both molecular and morphological signs of liver remodeling. Methods: A study was conducted on male C57BL/6J mice to assess the effect of 4- and 8-week HFDs (60% kcal from fat) on (I) liver steatosis and fibrosis, and (II) expression of factors involved in inflammation and angiogenesis. Results: After an 8-week HFD, vascular endothelial growth factor type-2 receptor (VEGF-R2) and fatty acid translocase/trombospondin-1 receptor (CD36) were overexpressed in liver tissue of mice given HFDs. These changes suggest impaired liver angiogenesis and occurred together with (I) increased GPR78-BiP and EIF2alpha phosphorylation, suggesting endoplasmic reticulum stress, (II) induction of Col1a1 gene expression, a marker of fibrosis, and (III) increased CD31 immunolabeling, consistent with active angiogenesis and fibrosis. Conclusion: Our data show that very HFDs promote a rapid inflammatory response, as well as deregulation of angiogenesis, both consistent with development of liver fibrosis
Antecedentes: El hígado graso no alcohólico (HGNA) es una enfermedad hepática que ocasiona fibrosis y se genera por la ingesta de dietas ricas en grasa. Aunque los efectos nocivos de este tipo de dietas son de gran interés, no son muy abundantes los estudios sistemáticos sobre las consecuencias que su consumo puede tener en el hígado. Objetivo: Evaluar los efectos de una dieta rica en grasa sobre el remodelado hepático, tanto a nivel morfológico como molecular. Métodos: Se utilizaron ratones macho C57BL/6J tratados durante 4/8 semanas con una dieta que contenía un 60% de las kilocalorías procedentes de grasa sobre: 1) la aparición de esteatosis y/o fibrosis hepática y 2) la expresión de factores implicados en procesos de inflamación y angiogénesis. Resultados: Tras 8 semanas de dieta se observó un incremento en el receptor del factor de crecimiento vascular endotelial tipo 2 (R2-FCVE) y en la translocasa de ácidos grasos (CD36). Estos cambios, que sugieren que los procesos angiogénicos del hígado están alterados, fueron simultáneos a: 1) un aumento del GPR78-BiP y de la fosforilación de EIF2alpha, marcadores de estrés del retículo endoplásmico, 2) la inducción en la expresión del gen de colágeno Col1a1, indicador de fibrosis y 3) un incremento de células inmunofluorescentes para CD31 compatible con procesos de angiogénesis y de fibrosis. Conclusiones: Nuestros resultados muestran que las dietas con alto contenido en grasa inducen la rápida activación de respuestas inflamatorias, así como alteraciones en la angiogénesis, siendo ambos procesos compatibles con el desarrollo de fibrosis hepática
Subject(s)
Animals , Mice , Dietary Fats/adverse effects , Diet, High-Fat/adverse effects , Angiogenesis Inhibitors , Fatty Liver/complications , Fatty Liver/veterinary , Inflammation/complications , Endothelial Growth Factors/administration & dosage , CD36 Antigens , Fibrosis , Research Design , Blotting, WesternABSTRACT
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a condition that leads to fibrosis, is caused by intake of very high-fat diets (HFDs). However, while the negative impact on the liver of these diets has been an issue of interest, systematic research on the effect of HFDs are lacking. OBJECTIVE: To characterize the overall impact of HFDs on both molecular and morphological signs of liver remodeling. METHODS: A study was conducted on male C57BL/6J mice to assess the effect of 4- and 8-week HFDs (60% kcal from fat) on (i) liver steatosis and fibrosis, and (ii) expression of factors involved in inflammation and angiogenesis. RESULTS: After an 8-week HFD, vascular endothelial growth factor type-2 receptor (VEGF-R2) and fatty acid translocase/trombospondin-1 receptor (CD36) were overexpressed in liver tissue of mice given HFDs. These changes suggest impaired liver angiogenesis and occurred together with (i) increased GPR78-BiP and EIF2α phosphorylation, suggesting endoplasmic reticulum stress, (ii) induction of Col1a1 gene expression, a marker of fibrosis, and (iii) increased CD31 immunolabeling, consistent with active angiogenesis and fibrosis. CONCLUSION: Our data show that very HFDs promote a rapid inflammatory response, as well as deregulation of angiogenesis, both consistent with development of liver fibrosis.
