Dietary sucrose is essential to the development of liver injury in the methionine-choline-deficient model of steatohepatitis.
J Lipid Res
; 50(10): 2072-82, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19295183
ABSTRACT
Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to study the pathophysiology of fatty liver disease in human beings. The most widely used commercial MCD formulas not only lack methionine and choline but also contain excess sucrose and fat. The objective of this study was to determine whether dietary sucrose in the MCD formula plays a role in the pathogenesis of MCD-related liver disease. We prepared two custom MCD formulas, one containing sucrose as the principal carbohydrate and the other substituting sucrose with starch. Mice fed the sucrose-enriched formula developed typical features of MCD-related liver disease, including hepatic steatosis, hepatocellular apoptosis, alanine aminotransferase elevation, lipid peroxidation, and hepatic inflammation. In contrast, mice fed MCD-starch were significantly protected against liver injury. MCD-sucrose and MCD-starch mice displayed identical diet-related abnormalities in hepatic fatty acid uptake and triglyceride secretion. Hepatic de novo lipogenesis and triglyceride synthesis, however, were 2 times higher in MCD-sucrose mice than MCD-starch mice (P < 0.01). Hepatic lipid analysis revealed accumulation of excess saturated fatty acids in MCD-sucrose mice that correlated with hepatocellular injury. Overall, the results indicate that dietary sucrose is critical to the pathogenesis of MCD-mediated steatohepatitis. They suggest that saturated fatty acids, which are products of de novo lipogenesis, are mediators of hepatic toxicity in this model of liver disease.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sacarosa
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Deficiencia de Colina
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Hígado Graso
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Hígado
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Metionina
Límite:
Animals
Idioma:
En
Revista:
J Lipid Res
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos