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Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers.

ABSTRACT: Apolipoprotein A5 (apoA5) is a potent regulator of triglyceride (TG) metabolism and therefore may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a disease characterised by excessive TG-rich lipid droplets in hepatocytes. To test this hypothesis, we examined the mRNA expression of apoA5 in paediatric NAFLD livers in comparison to healthy controls. According to microarray and quantitative real-time PCR, human NAFLD livers exhibited elevated apoA5 expression compared to healthy controls. The apoA5 expression levels were positively correlated with hepatic TG storage and a marker for lipid droplets (perilipin), but were not correlated with plasma TG levels. These observations were confirmed with a NAFLD rat model. Interestingly, apoA5 expression was not altered in cultured fat-laden HepG2 cells, demonstrating that fat storage does not induce apoA5 in NAFLD livers. Therefore, the correlation between apoA5 and intracellular fat storage is likely explained by the potent effect of apoA5 in promoting intracellular fat storage. Our NAFLD patients and rats had elevated insulin resistance, which may have a role in elevating apoA5 expression in NAFLD livers. Our data support the hypothesis that apoA5 promotes hepatic TG storage and therefore contributes to the pathogenesis of NAFLD, and may represent a potential target for therapeutic intervention.

SUBMITTER: Feng Q

PROVIDER: S-EPMC4427056 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers.

Feng Qin Q Baker Susan S SS Liu Wensheng W Arbizu Ricardo A RA Aljomah Ghanim G Khatib Maan M Nugent Colleen A CA Baker Robert D RD Forte Trudy M TM Hu Yiyang Y Zhu Lixin L

Pathology 20150601 4

Apolipoprotein A5 (apoA5) is a potent regulator of triglyceride (TG) metabolism and therefore may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a disease characterised by excessive TG-rich lipid droplets in hepatocytes. To test this hypothesis, we examined the mRNA expression of apoA5 in paediatric NAFLD livers in comparison to healthy controls. According to microarray and quantitative real-time PCR, human NAFLD livers exhibited elevated apoA5 expression compared t ...[more]

PMID: 25938357

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Project description:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression. The aim of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans. Animal models DD Shionogi (DS), Fatty Liver Shionogi (FLS Wild; W), and FLS ob/ob mice were subjected as the normal control, SS model and NASH model, respectively. Male DS mice (Riken BRC No. 03706) were provided by Riken bio-resource center through the national bio-resource project of Japan. Male FLS W and male FLS-ob/ob mice were obtained from Shionogi research laboratories (Shiga, Japan). Animals were housed in a room maintained at a controlled temperature of 24 Â± 2 Ë?C under a 12-h light-dark cycle. Animals were provided ad libitum access to water and standard pellet feed. Five male mice of every strain (24 weeks old; mean body weight of DS, FLS W and FLS-ob/ob were 31.1 Â± 1.1g, 38.4 Â± 3.4g and 56.0 Â± 5.0g, respectively) were sacrificed under pentobarbital anesthesia by whole blood collection from the right ventricle. The livers were cut into about 200 mg pieces and fixed in 10% formalin for histological analysis or fresh-frozen in liquid nitrogen and stored at -80 Â°C in a freezer until use. miRNA expression analysis Total RNAs in mouse liver were isolated using TrizolReagent (Life Technologies, California, USA) as described the manufacturerâ??s protocol. The quality of total RNA samples was checked by applying the RNA Integrity Number (RIN) which is calculated by a proprietary algorithm of the Agilent 2100 Bioanalyzer expert software (Agilent technologies, CA, USA). Only high quality RNA, with RNA integrity number (RIN) greater than 8 and A260/280 and A260/230 greater than 1.8, will be considered for microarray analysis. TaqManÂ® Array Rodent MicroRNA A Card v2.0 (Thermo Fisher Scientific, MA, USA) was used to assess 375 miRNA expression profiles in mouse liver tissue.

Dataset Information

Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers.

Publications

Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers.

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