A Diet-Induced Pediatric Model of Non Alcoholic Fatty Liver Disease Using Neonatal Iberian Pigs (OR26-02-19)
| Autor: | Douglas G. Burrin, Daniel A Columbus, Daniel G. Peterson, Matthew A. Burd, Gabriella V. Hernandez, Christopher L. Kitts, Michael R. La Frano, Mark S. Edwards, Kim A. Sprayberry, Rob Fanter, Margaret Rice, Rodrigo Manjarín, Magdalena Maj, Victoria Smith, Darin C. Bennet, Mieko Temple |
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| Rok vydání: | 2019 |
| Předmět: |
Liver injury
medicine.medical_specialty Nutrition and Dietetics business.industry Insulin medicine.medical_treatment Leptin Fatty liver Medicine (miscellaneous) Fructose medicine.disease chemistry.chemical_compound Experimental Animal Nutrition Endocrinology chemistry Lactate dehydrogenase Internal medicine medicine Homeostatic model assessment business Dyslipidemia Food Science |
| Zdroj: | Current Developments in Nutrition. 3:nzz033.OR26-02 |
| ISSN: | 2475-2991 |
| DOI: | 10.1093/cdn/nzz033.or26-02-19 |
| Popis: | OBJECTIVES: The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has increased over the past decades, creating a need for animal models that recapitulate the features of the pediatric disease. Iberian pigs have a leptin-resistant phenotype characterized by hyperleptinemia, hyperphagia, and extreme adipogenesis. We hypothesized that neonatal Iberian pigs fed a high-fat high-fructose (HFF) diet will develop a pattern of liver injury resembling pediatric NAFLD. In addition, we sought to determine if a mixture of probiotics would prevent the disease. METHODS: Animals were fed 1 of 4 diets containing (g/kg body weight × d) 0 g fructose, 11 g fat and 199 kcal (CON-N; n = 8), 22 g fructose, 16 g fat and 300 kcal (HFF-N; n = 6), CON + probiotic (CON-P; n = 6), or HFF + probiotic (HFF-P; n = 6) every 6 h for 70 d. The probiotic mixture (6.2 × 10(4)cfu/mL) contained Pediococcus, Lactobacillus and Bacillus. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 65 at 2 h post feeding. Fasting leptin, insulin, glucose and homeostatic model assessment (HOMA) values were assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and gene expression of tumor necrosis factor (TNF) α, tumor growth factor (TGF) β, interleukin (IL) 1α, peroxisome proliferator-activated receptor (PPAR) γ, carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein (SREBP) 1c. RESULTS: Body weight was higher in CON-P, and insulin and HOMA values in HFF-P and CON-P (P ≤ 0.05). Leptin, alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase and total bilirubin were increased (P ≤ 0.001), and high and low density lipoproteins decreased (P ≤ 0.05) in HFF-N and HFF-P. Livers in HFF-P and HFF-N had higher relative weight and TG (P ≤ 0.001), micro and macrovesicular steatosis, ballooning degeneration, Mallory-denk bodies, inflammation and necrosis, increased gene expression of TNFα, TGFβ, IL1α and PPARγ (P ≤ 0.001), and decreased ChREBP (P ≤ 0.001). CONCLUSIONS: Iberian pigs fed a HFF diet recapitulate many pediatric NAFLD-associated features, in the absence of obesity and independently of probiotic supplementation, suggesting a potentially suitable model for pediatric NAFLD research. FUNDING SOURCES: ARI, AcornSeekers. |
| Databáze: | OpenAIRE |
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