Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model

Oishi, Toshiyuki; Terai, Shuji; Kuwashiro, Shinya; Fujisawa, Koichi; Matsumoto, Toshihiko; Nishina, Hiroshi; Sakaida, Isao

doi:10.1016/j.bbrc.2012.04.087

Cited by 11 publications

(8 citation statements)

References 18 publications

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“…All of these components except for hypertension were recognized in the HFD-medaka, as previously reported [4,5,6]. Several kinds of glomerular disease can be induced in metabolic syndrome patients, including diabetes nephropathy, FSGS, and ORG.…”

Section: Discussionsupporting

confidence: 62%

“…In this condition, medaka adult that are fed HFD (HFD-medaka) consistently exhibit a fatty liver and subsequently develop non-alcoholic steatohepatitis (NASH) [4]. Using this system, several useful drugs for NASH were found [4,5,6]. In humans, non-alcoholic fat liver disease followed by NASH initially cause chronic liver dysfunction that may later progress to liver cirrhosis and ultimately hepatocellular carcinoma, and thus new guideline of NASH was developed [7].…”

Section: Introductionmentioning

confidence: 99%

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Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy

Ichimura

Kawashima

Nakamura

et al. 2013

Biochemical and Biophysical Research Communications

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Obesity, an ongoing significant public health problem, is a part of complex disease characterized as metabolic syndrome. Medaka and zebrafish are useful aquatic experimental animals widely used in the field of toxicology and environmental health sciences and as a human disease models. In medaka, simple feeding of a high fat diet (HFD) can induce body weight gain, excessive accumulation of visceral adipose tissue, hyperglycemia, hyperlipidemia, and steatohepatists, which mimics human metabolic syndrome. In the present study, to explore the possibility that the adult medaka fed with HFD (HFD-medaka) can be used as an animal model for human metabolic syndrome-associated glomerular disease, including obesity-related glomerulopathy (ORG), we analyzed structural alterations and protein expression in the mesonephric kidney of HFD-medaka. We found that the histopathology was consistent with glomerulomegaly accompanied by the dilation of glomerular capillaries and proliferative expansion of the mesangium, a condition partially comparable to human ORG. Moreover, expressions of several kinds of kidney disease-related proteins (such as MYH9, SM22α) were significantly elevated. Thus, the HFD-medaka has a high potential as an animal model useful for exploring the mechanism underling human ORG.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy

Ichimura

Kawashima

Nakamura

et al. 2013

Biochemical and Biophysical Research Communications

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“…Thus, NASH can be induced in medaka by a HFD, and the proportion of n-3 PUFAs in the liver affects NASH pathogenesis in these fish. Subsequent work has confirmed that this medaka NASH model is helpful for advancing our understanding of human NASH pathology and can assist in the clinical development of novel therapeutics, as described below (Kuwashiro et al, 2011; Oishi et al, 2012). …”

Section: Dietary Fish Modelsmentioning

confidence: 74%

The expanding role of fish models in understanding non-alcoholic fatty liver disease

Asaoka

Terai

Sakaida

et al. 2013

Disease Models &Amp; Mechanisms

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Non-alcoholic fatty liver disease (NAFLD) is a condition in which excessive fat accumulates in the liver of an individual who has not consumed excessive alcohol. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to hepatic cirrhosis and/or hepatocellular carcinoma (HCC). NAFLD is considered to be a hepatic manifestation of metabolic syndrome, and its incidence has risen worldwide in lockstep with the increased global prevalence of obesity. Over the last decade, rodent studies have yielded an impressive list of molecules associated with NAFLD and NASH pathogenesis. However, the identification of currently unknown metabolic factors using mammalian model organisms is inefficient and expensive compared with studies using fish models such as zebrafish (Danio rerio) and medaka (Oryzias latipes). Substantial advances in unraveling the molecular pathogenesis of NAFLD have recently been achieved through unbiased forward genetic screens using small fish models. Furthermore, these easily manipulated organisms have been used to great advantage to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD. In this Review, we summarize aspects of NAFLD (specifically focusing on NASH) pathogenesis that have been previously revealed by rodent models, and discuss how small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism. We describe the various types of fish models in use for this purpose, including those generated by mutation, transgenesis, or dietary or chemical treatment, and contrast them with rodent models. The use of small fish in identifying novel potential therapeutic agents for the treatment of NAFLD and NASH is also addressed.

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“…cDNAs were synthesized using purified RNA plus random hexamers and the Transcriptor First Strand cDNA synthesis kit (Roche, Indianapolis, IN). Quantitative real-time RT-PCR was performed as described, and primers sequences were written in the report 7 .…”

Section: Methodsmentioning

confidence: 99%

“…Of significance to our study, a high-fat diet (HFD)-fed medaka model has been established 6, 7 . It has previously been reported that drug assessment using a HFD-fed medaka model is feasible 8 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effects of L-carnitine on medaka (Oryzias latipes) fatty liver

Fujisawa

Takami

Matsuzaki

et al. 2017

Sci Rep

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Lifestyle-related diseases have become a major issue in recent years. The increasing incidence of fatty liver underlines the urgency with which the issues of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) need to be addressed. L-carnitine is a compound known to transport fatty acids into the mitochondria to enhance β-oxidation-mediated metabolism of fats. In this study, the effects of L-carnitine administration on fatty liver of medaka (Oryzias latipes) were analysed, to check for disease improvement and metabolic changes. Additionally, the effects of the concomitant administration of L-carnitine and eicosapentaenoic acid (20:5n-3) (EPA) were investigated. Findings indicated reduced lipid deposition, increase in metabolites associated with β-oxidation, and significant reduction in fatty acid levels in the liver, implying improvement in fatty liver condition. Concomitant administration of L-carnitine and EPA resulted in further benefits, via changes in fatty acid composition in the medaka fatty liver model.

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Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model

Cited by 11 publications

References 18 publications

Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy

Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy

The expanding role of fish models in understanding non-alcoholic fatty liver disease

Evaluation of the effects of L-carnitine on medaka (Oryzias latipes) fatty liver

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