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Non-alcoholic Steatohepatitis following feeding of high polyunsaturated fat diets

ABSTRACT: Most commonly used models of non-alcoholic steatohepatitis (NASH) are diets based on specific gene knockouts or represent extreme manipulations of diet. We have examined the effects of modest increased caloric intake and high dietary unsaturated fat content on the development of NASH in male rats using a model in which overfeeding is accomplished via intragastric infusion of liquid diets as a part of total enteral nutrition. Male Sprague dawley rats were fed diets 5% corn oil containing diets at 187 Kcal/kg3/4/d or fed 70% corn oil containing diets at 220 Kcal/kg3/4/d for a period of 3 weeks. Hepatic gene expression were assessed at the end of the study. Our results indicate that overfeeding of high unsaturated fat diets leads to pathological, endocrine and metabolic changes characteristic of NASH patients and is associated with increased oxidative stress and TNF-a. Keywords: Steatosis and unsaturated fat

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE8253 | GEO | 2008/05/19

SECONDARY ACCESSION(S): PRJNA101201

REPOSITORIES: GEO

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Project description:PURPOSE: Previous mouse studies using corn oil (Ï?-6) as the dietary fat source suggest that decreasing dietary fat content can slow prostate cancer (PCa) growth. However, other studies, in which the diet was composed around saturated fat, showed no difference in outcomes between high-fat and low-fat diets. The relative effects of other fats, such as fish oil and olive oil, also remain unexplored. To our knowledge, no trial has yet compared the effect of various fats on prostate cancer progression. Therefore, we sought to systematically study the effect of fish oil, olive oil, corn oil, and saturated fat on prostate cancer progression. METHODS: A total of 96 male SCID mice were injected with LAPC-4 human PCa cells. Two weeks following injection, mice were singly-housed and randomized to either a fish oil, olive oil, corn oil, or saturated fat based diet. Animals were euthanized when tumors reached 1,000 mm3. Serum was collected at sacrifice and assayed for PSA, insulin, IGF-1, IGFBP-3, and PGE-2 levels. Tumors were also assayed for PGE-2, and COX-2 levels, and gene array analysis was performed. RESULTS: Mice weights and tumor volumes were equivalent across groups at randomization. Overall, fish-oil consumption was associated with improved survival, relative to all other dietary groups (Log-rank, all p<0.05). We did not detect any significant difference in serum PSA, insulin, IGF-1, IGFBP-3, and PGE-2 levels. Glucose at the time of sacrifice was statistically different between groups, with the fish-oil fed mice having the highest levels of serum glucose (Kruskal-Wallis, p=0.03). CONCLUSIONS: In this prostate cancer xenograft model, we found that consuming a diet in which fish-oil was the only fat source slowed tumor growth in improved survival, compared to mice consuming diets composed of olive oil, corn oil, or saturated fat sources. These results suggest that type of dietary fat consumed may be as important as amount of dietary fat consumed in the setting of prostate cancer. DESIGN: A total of 96 male SCID mice were injected with LAPC-4 human prostate cancer cells. After 2 weeks of tumor growth, the mice were randomized to one of four diets: corn oil, fish oil, olive oil, and saturated fat source diets. Animals were euthanized when tumor volumes exceeded 1000 mm^3. Sera and tissues from the median 6 surviving animals from each of the four dietary groups were analyzed.

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Non-alcoholic Steatohepatitis following feeding of high polyunsaturated fat diets

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