RRC ID 12306
Author Matsumoto T, Terai S, Oishi T, Kuwashiro S, Fujisawa K, Yamamoto N, Fujita Y, Hamamoto Y, Furutani-Seiki M, Nishina H, Sakaida I.
Title Medaka as a model for human nonalcoholic steatohepatitis.
Journal Dis Model Mech
Abstract The global incidence of nonalcoholic steatohepatitis (NASH) is increasing and current mammalian models of NASH are imperfect. We have developed a NASH model in the ricefish medaka (Oryzias latipes), which is based on feeding the fish a high-fat diet (HFD). Medaka that are fed a HFD (HFD-medaka) exhibited hyperlipidemia and hyperglycemia, and histological examination of the liver revealed ballooning degeneration. The expression of lipogenic genes (SREBP-1c, FAS and ACC1) was increased, whereas the expression of lipolytic genes (PPARA and CPT1) was decreased. With respect to liver fatty acid composition, the concentrations of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs had declined and the n-3:n-6 ratio was reduced. Treatment of HFD-medaka with the n-3 PUFA eicosapentaenoic acid (EPA) mitigated disease, as judged by the restoration of normal liver fatty acid composition and normal expression levels of lipogenic and lipolytic genes. Moreover, medaka that were fed a diet deficient in n-3 PUFAs developed NASH features. Thus, NASH can be induced in medaka by a HFD, and the proportion of n-3 PUFAs in the liver influences the progress of NASH pathology in these fish. Our model should prove helpful for the dissection of the causes of human NASH and for the design of new and effective therapies.
Volume 3(7-8)
Pages 431-40
Published 2010-7
DOI 10.1242/dmm.002311
PII dmm.002311
PMID 20371730
MeSH Animals Dietary Fats / administration & dosage Dietary Fats / pharmacology Disease Models, Animal* Eicosapentaenoic Acid / administration & dosage Eicosapentaenoic Acid / pharmacology Fatty Liver / complications Fatty Liver / pathology* Gene Expression Regulation / drug effects Humans Hyperglycemia / complications Hyperglycemia / pathology Hyperlipidemias / complications Hyperlipidemias / pathology Lipogenesis / drug effects Lipogenesis / genetics Liver / drug effects Liver / pathology Oryzias / metabolism* Phenotype
IF 4.028
Times Cited 22
Medaka Cab