Liver injury and fibrosis induced by dietary challenge in the Ossabaw miniature Swine. 2015

Tiebing Liang, and Mouhamad Alloosh, and Lauren N Bell, and Allison Fullenkamp, and Romil Saxena, and William Van Alstine, and Phelan Bybee, and Klára Werling, and Michael Sturek, and Naga Chalasani, and Howard C Masuoka
Department of Medicine, Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

BACKGROUND Ossabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model. METHODS Ossabaw swine were fed standard chow (control group; n = 6) or NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24. RESULTS The NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c) Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides. CONCLUSIONS This report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides.

UI MeSH Term Description Entries
D008103 Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004041 Dietary Fats Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. Fats, Dietary,Dietary Fat,Fat, Dietary
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D005632 Fructose A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding. Levulose,Apir Levulosa,Fleboplast Levulosa,Levulosa,Levulosa Baxter,Levulosa Braun,Levulosa Grifols,Levulosa Ibys,Levulosa Ife,Levulosa Mein,Levulosado Bieffe Medit,Levulosado Braun,Levulosado Vitulia,Plast Apyr Levulosa Mein,Levulosa, Apir,Levulosa, Fleboplast
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D013556 Swine, Miniature Genetically developed small pigs for use in biomedical research. There are several strains - Yucatan miniature, Sinclair miniature, and Minnesota miniature. Miniature Swine,Minipigs,Miniature Swines,Minipig,Swines, Miniature
D056486 Chemical and Drug Induced Liver Injury A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment. Drug-Induced Liver Injury,Liver Injury, Drug-Induced,Acute Liver Injury, Drug-Induced,Chemically-Induced Liver Toxicity,Drug-Induced Acute Liver Injury,Drug-Induced Liver Disease,Hepatitis, Drug-Induced,Hepatitis, Toxic,Liver Injury, Drug-Induced, Acute,Toxic Hepatitis,Acute Liver Injury, Drug Induced,Chemically Induced Liver Toxicity,Chemically-Induced Liver Toxicities,Disease, Drug-Induced Liver,Diseases, Drug-Induced Liver,Drug Induced Acute Liver Injury,Drug Induced Liver Disease,Drug Induced Liver Injury,Drug-Induced Hepatitides,Drug-Induced Hepatitis,Drug-Induced Liver Diseases,Drug-Induced Liver Injuries,Hepatitides, Drug-Induced,Hepatitides, Toxic,Hepatitis, Drug Induced,Injuries, Drug-Induced Liver,Injury, Drug-Induced Liver,Liver Disease, Drug-Induced,Liver Diseases, Drug-Induced,Liver Injuries, Drug-Induced,Liver Injury, Drug Induced,Liver Toxicities, Chemically-Induced,Liver Toxicity, Chemically-Induced,Toxic Hepatitides,Toxicities, Chemically-Induced Liver,Toxicity, Chemically-Induced Liver

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