Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease
| Autor: | Fiorella Piemonte, Letizia Da Sacco, Valerio Nobili, Rita De Vito, Nadia Panera, Anna Alisi, Andrea Masotti, Giovannella Bruscalupi, Gian Franco Bottazzo, Silvia Leoni |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
microrna Blotting Western steatohepatitis Fructose nafld Carbohydrate metabolism Pathology and Forensic Medicine Rats Sprague-Dawley Pathogenesis Downregulation and upregulation Internal medicine Nonalcoholic fatty liver disease medicine targets Animals PTEN Gene silencing Molecular Biology Analysis of Variance biology Reverse Transcriptase Polymerase Chain Reaction Body Weight Cell Biology Microarray Analysis medicine.disease Dietary Fats Immunohistochemistry Diet Rats Fatty Liver MicroRNAs Endocrinology Gene Expression Regulation Liver Biochemistry biology.protein Steatohepatitis Steatosis |
| Zdroj: | Laboratory Investigation. 91:283-293 |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/labinvest.2010.166 |
| Popis: | Nonalcoholic fatty liver disease (NAFLD) is an emerging disease with a broad spectrum of liver conditions. The complex molecular pathogenesis of NAFLD is still unclear. In this study, we conducted an analysis of microRNA (miRNA) expression profiles in liver of rats made NAFLD by different diets. To this aim, Sprague-Dawley rats were fed ad libitum for 3 months with different diets: standard diet (SD), diet enriched in fats and low in carbohydrates (HFD), SD with high fructose (SD-HF) and diet with high levels of fats and fructose (HFD-HF). Our results demonstrated that the treatment with different dietetic regimens caused a significant increase of the body weight and the alteration of some metabolic parameters compared with control animals, as well as various liver injuries. The miRNAs analysis showed the significant downregulation of three miRNAs (miR-122, miR-451 and miR-27) and the upregulation of miR-200a, miR-200b and miR-429 in HFD, SD-HF and HFD-HF rats. Besides, miR-21 expression was significantly decreased only in fructose-enriched diets. These miRNAs target molecules involved in the control of lipid and carbohydrate metabolism, signal transduction, cytokine and chemokine-mediated signaling pathway and apoptosis. Western blot analysis of PKCδ, LITAF, ALDOLASE-A, p38MAPK, PTEN, LIPIN1, EPHRIN-A1, EPHA2 and FLT1 showed a diet-induced deregulation of all these proteins. Interestingly, the expression pattern of LITAF, PTEN, LIPIN1, EPHRIN-A1, EPHA2 and FLT1 might be well explained by the trend of their specific mRNAs, by potentially regulatory miRNAs, or both. In conclusion, we highlight for the first time the potential involvement of novel determinants (miRNAs and proteins) in the molecular pathogenesis of diet-induced NAFLD. |
| Databáze: | OpenAIRE |
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