Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease
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...
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| creator | Alisi, Anna Da Sacco, Letizia Bruscalupi, Giovannella Piemonte, Fiorella Panera, Nadia De Vito, Rita Leoni, Silvia Bottazzo, Gian Franco Masotti, Andrea Nobili, Valerio |
| description | 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. |
| doi_str_mv | 10.1038/labinvest.2010.166 |
| format | Article |
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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.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/labinvest.2010.166</identifier><identifier>PMID: 20956972</identifier><identifier>CODEN: LAINAW</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>631/208/199 ; 631/337/384/331 ; 631/80/304 ; 692/699/1503/1607/2750 ; Analysis of Variance ; Animals ; Biological and medical sciences ; Biotechnology ; Blotting, Western ; Body Weight ; Diet ; Dietary Fats ; Fatty Liver - genetics ; Fatty Liver - physiopathology ; Fructose ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Regulation - physiology ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Laboratory Medicine ; Liver - metabolism ; Liver - pathology ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Medicine ; Medicine & Public Health ; Microarray Analysis ; microRNA ; MicroRNAs - metabolism ; NAFLD ; Other diseases. Semiology ; Pathology ; Rats ; Rats, Sprague-Dawley ; research-article ; Reverse Transcriptase Polymerase Chain Reaction ; steatohepatitis ; targets</subject><ispartof>Laboratory investigation, 2011-02, Vol.91 (2), p.283-293</ispartof><rights>2011 United States & Canadian Academy of Pathology</rights><rights>United States and Canadian Academy of Pathology, Inc. 2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Feb 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c597t-c9ef47860a25fa8020b6ed44d56fcfec9bcc28b89bfadb0431aefd79c31919d43</citedby><cites>FETCH-LOGICAL-c597t-c9ef47860a25fa8020b6ed44d56fcfec9bcc28b89bfadb0431aefd79c31919d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23908433$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20956972$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alisi, Anna</creatorcontrib><creatorcontrib>Da Sacco, Letizia</creatorcontrib><creatorcontrib>Bruscalupi, Giovannella</creatorcontrib><creatorcontrib>Piemonte, Fiorella</creatorcontrib><creatorcontrib>Panera, Nadia</creatorcontrib><creatorcontrib>De Vito, Rita</creatorcontrib><creatorcontrib>Leoni, Silvia</creatorcontrib><creatorcontrib>Bottazzo, Gian Franco</creatorcontrib><creatorcontrib>Masotti, Andrea</creatorcontrib><creatorcontrib>Nobili, Valerio</creatorcontrib><title>Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>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.</description><subject>631/208/199</subject><subject>631/337/384/331</subject><subject>631/80/304</subject><subject>692/699/1503/1607/2750</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Blotting, Western</subject><subject>Body Weight</subject><subject>Diet</subject><subject>Dietary Fats</subject><subject>Fatty Liver - genetics</subject><subject>Fatty Liver - physiopathology</subject><subject>Fructose</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. 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Semiology</subject><subject>Pathology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>research-article</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>steatohepatitis</subject><subject>targets</subject><issn>0023-6837</issn><issn>1530-0307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU9vFCEYxonR2LX6BTwYYmI9TWVg_kDSi2nqn6TGi54nDLx0aRhYgZlk_fSyzrpNPPREAr_n9wIPQq9rclkTxj84OVq_QMqXlBz2uu4J2tQtIxVhpH-KNoRQVnWc9WfoRUr3hNRN07XP0Rklou1ETzfo9zcbfZgASy_dPtmEIywgXcI-LODwFByo2cmINWSIk_XS54Stx3kLeCfzNtyBh0MwGKwt5Mp6PSvQRVCUKmyDswobmfMeO7tAMdkEMsFL9MyUQfDquJ6jn59uflx_qW6_f_56_fG2Uq3oc6UEmKbnHZG0NZITSsYOdNPotjPKgBKjUpSPXIxG6pE0rJZgdC8Uq0UtdMPO0fvVu4vh11y-a5hsUuCc9BDmNPCGc1oTwQv59j_yPsyxvOIv1LaEN7RAdIVUDClFMMMu2knG_VCT4dDLcOplOPQylF5K6M3RPI8T6FPkXxEFeHcEZFLSmSi9sumBY6IMZ6xwbOVSOfJ3EB-u-Oj4izXlZZ4jnLQn9ECu4NUKQilksUWflAVf6rQRVB50sI_N-QMd_s_O</recordid><startdate>20110201</startdate><enddate>20110201</enddate><creator>Alisi, Anna</creator><creator>Da Sacco, Letizia</creator><creator>Bruscalupi, Giovannella</creator><creator>Piemonte, Fiorella</creator><creator>Panera, Nadia</creator><creator>De Vito, Rita</creator><creator>Leoni, Silvia</creator><creator>Bottazzo, Gian Franco</creator><creator>Masotti, Andrea</creator><creator>Nobili, Valerio</creator><general>Elsevier Inc</general><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20110201</creationdate><title>Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease</title><author>Alisi, Anna ; Da Sacco, Letizia ; Bruscalupi, Giovannella ; Piemonte, Fiorella ; Panera, Nadia ; De Vito, Rita ; Leoni, Silvia ; Bottazzo, Gian Franco ; Masotti, Andrea ; Nobili, Valerio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c597t-c9ef47860a25fa8020b6ed44d56fcfec9bcc28b89bfadb0431aefd79c31919d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/208/199</topic><topic>631/337/384/331</topic><topic>631/80/304</topic><topic>692/699/1503/1607/2750</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Blotting, Western</topic><topic>Body Weight</topic><topic>Diet</topic><topic>Dietary Fats</topic><topic>Fatty Liver - genetics</topic><topic>Fatty Liver - physiopathology</topic><topic>Fructose</topic><topic>Fundamental and applied biological sciences. 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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.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>20956972</pmid><doi>10.1038/labinvest.2010.166</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/208/199 631/337/384/331 631/80/304 692/699/1503/1607/2750 Analysis of Variance Animals Biological and medical sciences Biotechnology Blotting, Western Body Weight Diet Dietary Fats Fatty Liver - genetics Fatty Liver - physiopathology Fructose Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation - physiology Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Laboratory Medicine Liver - metabolism Liver - pathology Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Medicine Medicine & Public Health Microarray Analysis microRNA MicroRNAs - metabolism NAFLD Other diseases. Semiology Pathology Rats Rats, Sprague-Dawley research-article Reverse Transcriptase Polymerase Chain Reaction steatohepatitis targets |
| title | Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease |
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