Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers
Autor: | Yi-Yang Hu, Ghanim Aljomah, Trudy M. Forte, Qin Feng, Lixin Zhu, Wensheng Liu, Susan S. Baker, Robert D. Baker, Maan Khatib, Ricardo A. Arbizu, Colleen A. Nugent |
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Rok vydání: | 2015 |
Předmět: |
Male
medicine.medical_specialty Adolescent Microarray Blotting Western Biology Real-Time Polymerase Chain Reaction Article Pathology and Forensic Medicine Rats Sprague-Dawley Pathogenesis chemistry.chemical_compound Non-alcoholic Fatty Liver Disease Internal medicine Lipid droplet medicine Animals Humans Child Apolipoproteins A Oligonucleotide Array Sequence Analysis Triglyceride Fatty liver nutritional and metabolic diseases Hep G2 Cells Metabolism medicine.disease digestive system diseases Rats Apolipoproteins Endocrinology chemistry Apolipoprotein A-V Perilipin Female Intracellular |
Zdroj: | Pathology. 47:341-348 |
ISSN: | 0031-3025 |
DOI: | 10.1097/pat.0000000000000251 |
Popis: | Summary Apolipoprotein A5 (apoA5) is a potent regulator of triglyceride (TG) metabolism and therefore may contribute to the patho-genesis 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. |
Databáze: | OpenAIRE |
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