LIVER MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN IN A RAT MODEL OF NONALCOHOLIC FATTY LIVER DISEASE: 95

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Excerpt

Nonalcoholic fatty liver (NAFLD) is one of the most common liver diseases encountered in the United States. A net retention of lipids within the hepatocytes is a prerequisite for the development of NAFLD. The metabolic anomalies responsible for lipid accumulation are not clear. Microsomal triglyceride transfer protein (MTP) plays an important role in lipoprotein assembly and lipid transport. We hypothesize that NAFLD is associated with a decreased MTP activity with a subsequent failure to mobilize lipids from the hepatocytes resulting in a net retention of fat. We tested our hypothesis in a SD rat-model of NAFLD described by Lieber et al. After three weeks on either a standard or a high fat-diet, (n = 6 per group) rats were sacrificed; liver tissue and whole blood were collected. Plasma and liver lipid levels were determined by enzymatic assay kits, MTP activity was measured by a fluorescent assay as described by Athar et al. As shown in table, rats fed a high fat diet had an increased cholesterol and triglyceride (TG) liver content, and a decreased plasma TG level as compared to controls; on the other hand, liver MTP activity was similar in both groups. Thus liver MTP does not appear to play a significant role in the development of steatosis in this specific animal model of NAFLD. Additional mechanisms such as the role of mitochondrial β-oxidation and reactive oxygen species are now being investigated.

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