Differential expression of intermediate filaments in the process of developing hepatic steatosis

Obesity causes changes in fatty acid metabolism that consequently leads to fatty liver. To identify the possible proteins involved in the processes of obesity, we performed a proteomic analysis of obesity‐induced mouse liver. Male C57BL/6J mice that were fed a high‐fat diet (HFD) for 24 wk, develope...

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Veröffentlicht in:Proteomics (Weinheim) 2011-07, Vol.11 (14), p.2777-2789
Hauptverfasser: Park, Jung-Eun, Kim, Hyun Tae, Lee, Sujin, Lee, Ye-Suk, Choi, Ung-Kyu, Kang, Jeong Han, Choi, Soo Young, Kang, Tae-Cheon, Choi, Myung-Sook, Kwon, Oh-Shin
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container_issue 14
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container_title Proteomics (Weinheim)
container_volume 11
creator Park, Jung-Eun
Kim, Hyun Tae
Lee, Sujin
Lee, Ye-Suk
Choi, Ung-Kyu
Kang, Jeong Han
Choi, Soo Young
Kang, Tae-Cheon
Choi, Myung-Sook
Kwon, Oh-Shin
description Obesity causes changes in fatty acid metabolism that consequently leads to fatty liver. To identify the possible proteins involved in the processes of obesity, we performed a proteomic analysis of obesity‐induced mouse liver. Male C57BL/6J mice that were fed a high‐fat diet (HFD) for 24 wk, developed hepatic steatosis characterized by considerable increase in free fatty acid (FFA) and triglyceride levels. Body weights were measured weekly and other measurements at weeks 2, 6, 12, 16, and 24. 2‐D‐based proteomic analysis revealed that, compared with the normal diet (ND) (n=50), high‐fat diet (n=50) changed the expression of 12 protein (8 up and 4 downregulated, by a 1.5× fold change and more, p
doi_str_mv 10.1002/pmic.201000544
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To identify the possible proteins involved in the processes of obesity, we performed a proteomic analysis of obesity‐induced mouse liver. Male C57BL/6J mice that were fed a high‐fat diet (HFD) for 24 wk, developed hepatic steatosis characterized by considerable increase in free fatty acid (FFA) and triglyceride levels. Body weights were measured weekly and other measurements at weeks 2, 6, 12, 16, and 24. 2‐D‐based proteomic analysis revealed that, compared with the normal diet (ND) (n=50), high‐fat diet (n=50) changed the expression of 12 protein (8 up and 4 downregulated, by a 1.5× fold change and more, p&lt;0.05). The most pronounced difference was observed in intermediate microfilament (IF) cytoskeleton proteins. In particular, vimentin (vim) as well as cytokeratins (CK‐8 and CK‐18) were significantly upregulated in obese animals. Moreover, the level of caspase‐generated IF fragment was also positively correlated with the degree of steatosis. The results suggest a significant alteration in IF organization during the development of hepatic steatosis leading to inflammation. The expression profile of selected proteins including vim was validated by Western blot, microarray analysis, and hepatocyte morphology by immunohistochemistry. Our results suggest that vim, like CK‐18, may be a useful marker for predicting obesity and liver disease.</description><identifier>ISSN: 1615-9853</identifier><identifier>ISSN: 1615-9861</identifier><identifier>ISSN: 1862-8346</identifier><identifier>EISSN: 1615-9861</identifier><identifier>DOI: 10.1002/pmic.201000544</identifier><identifier>PMID: 21674798</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Analytical, structural and metabolic biochemistry ; Animal proteomics ; Animals ; Biological and medical sciences ; Body weight ; Cytokeratin ; Cytoskeleton ; Diet ; Dietary Fats ; Fatty acids ; Fatty liver ; Fatty Liver - metabolism ; Fatty Liver - physiopathology ; Fatty liver disease ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Profiling ; Hepatocytes ; Hepatocytes - chemistry ; Hepatocytes - cytology ; Hepatocytes - metabolism ; High fat diet ; Humans ; Immunohistochemistry ; Inflammation ; Intermediate filament ; Intermediate filaments ; Intermediate Filaments - metabolism ; Keratins - genetics ; Keratins - metabolism ; Lipid Metabolism ; Liver - chemistry ; Liver - cytology ; Liver - metabolism ; Liver - pathology ; Liver diseases ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Mass Spectrometry - methods ; Medical sciences ; Metabolic diseases ; Metabolism ; Mice ; Mice, Inbred C57BL ; Microarray Analysis ; Microfilaments ; Miscellaneous ; Obesity ; Obesity - physiopathology ; Other diseases. Semiology ; Proteins ; Proteome - analysis ; proteomics ; Proteomics - methods ; Random Allocation ; steatosis ; Triglycerides ; Two-Dimensional Difference Gel Electrophoresis - methods ; Vimentin ; Vimentin - genetics ; Vimentin - metabolism ; Western blotting</subject><ispartof>Proteomics (Weinheim), 2011-07, Vol.11 (14), p.2777-2789</ispartof><rights>Copyright © 2011 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.</rights><rights>Copyright © 2011 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6034-c3dd56683f090f652bc492b5b786c5fb367726c85dc166bc9e55aea6102db1703</citedby><cites>FETCH-LOGICAL-c6034-c3dd56683f090f652bc492b5b786c5fb367726c85dc166bc9e55aea6102db1703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpmic.201000544$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpmic.201000544$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=24336577$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21674798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Jung-Eun</creatorcontrib><creatorcontrib>Kim, Hyun Tae</creatorcontrib><creatorcontrib>Lee, Sujin</creatorcontrib><creatorcontrib>Lee, Ye-Suk</creatorcontrib><creatorcontrib>Choi, Ung-Kyu</creatorcontrib><creatorcontrib>Kang, Jeong Han</creatorcontrib><creatorcontrib>Choi, Soo Young</creatorcontrib><creatorcontrib>Kang, Tae-Cheon</creatorcontrib><creatorcontrib>Choi, Myung-Sook</creatorcontrib><creatorcontrib>Kwon, Oh-Shin</creatorcontrib><title>Differential expression of intermediate filaments in the process of developing hepatic steatosis</title><title>Proteomics (Weinheim)</title><addtitle>Proteomics</addtitle><description>Obesity causes changes in fatty acid metabolism that consequently leads to fatty liver. To identify the possible proteins involved in the processes of obesity, we performed a proteomic analysis of obesity‐induced mouse liver. Male C57BL/6J mice that were fed a high‐fat diet (HFD) for 24 wk, developed hepatic steatosis characterized by considerable increase in free fatty acid (FFA) and triglyceride levels. Body weights were measured weekly and other measurements at weeks 2, 6, 12, 16, and 24. 2‐D‐based proteomic analysis revealed that, compared with the normal diet (ND) (n=50), high‐fat diet (n=50) changed the expression of 12 protein (8 up and 4 downregulated, by a 1.5× fold change and more, p&lt;0.05). The most pronounced difference was observed in intermediate microfilament (IF) cytoskeleton proteins. In particular, vimentin (vim) as well as cytokeratins (CK‐8 and CK‐18) were significantly upregulated in obese animals. Moreover, the level of caspase‐generated IF fragment was also positively correlated with the degree of steatosis. The results suggest a significant alteration in IF organization during the development of hepatic steatosis leading to inflammation. The expression profile of selected proteins including vim was validated by Western blot, microarray analysis, and hepatocyte morphology by immunohistochemistry. Our results suggest that vim, like CK‐18, may be a useful marker for predicting obesity and liver disease.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animal proteomics</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Body weight</subject><subject>Cytokeratin</subject><subject>Cytoskeleton</subject><subject>Diet</subject><subject>Dietary Fats</subject><subject>Fatty acids</subject><subject>Fatty liver</subject><subject>Fatty Liver - metabolism</subject><subject>Fatty Liver - physiopathology</subject><subject>Fatty liver disease</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Profiling</subject><subject>Hepatocytes</subject><subject>Hepatocytes - chemistry</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - metabolism</subject><subject>High fat diet</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Intermediate filament</subject><subject>Intermediate filaments</subject><subject>Intermediate Filaments - metabolism</subject><subject>Keratins - genetics</subject><subject>Keratins - metabolism</subject><subject>Lipid Metabolism</subject><subject>Liver - chemistry</subject><subject>Liver - cytology</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver diseases</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Mass Spectrometry - methods</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microarray Analysis</subject><subject>Microfilaments</subject><subject>Miscellaneous</subject><subject>Obesity</subject><subject>Obesity - physiopathology</subject><subject>Other diseases. Semiology</subject><subject>Proteins</subject><subject>Proteome - analysis</subject><subject>proteomics</subject><subject>Proteomics - methods</subject><subject>Random Allocation</subject><subject>steatosis</subject><subject>Triglycerides</subject><subject>Two-Dimensional Difference Gel Electrophoresis - methods</subject><subject>Vimentin</subject><subject>Vimentin - genetics</subject><subject>Vimentin - metabolism</subject><subject>Western blotting</subject><issn>1615-9853</issn><issn>1615-9861</issn><issn>1862-8346</issn><issn>1615-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0UlvFDEQBlALgUgIXDmilhAKlx68L0c0hBCRAJFYjsbtLhOH3rB7IPn3eDTDgDgQTrasV-VSfQg9JHhBMKbPpj76BcXljgXnt9A-kUTURktye3cXbA_dy_kSY6K0UXfRHiVScWX0Pvr8IoYACYY5uq6CqylBznEcqjFUcZgh9dBGN0MVYuf6wnJ5ruYLqKY0-mLXsIXv0I1THL5UFzC5Ofoqz-DmMcd8H90JrsvwYHseoA8vj94vX9Wnb49Pls9Pay8x47VnbSuk1Cxgg4MUtPHc0EY0SksvQsOkUlR6LVpPpGy8ASEcOEkwbRuiMDtAh5u-Za5vK8iz7WP20HVugHGVrSEaC2yMvlFqzTDFlP6HVJxrgiUr8uk_JSmrN5oKYQp9_Be9HFdpKLuxRBDFmSqxFbXYKJ_GnBMEO6XYu3RdWtl18nadvN0lXwoebduumpLZjv-KuoAnW-Cyd11IbvAx_3acMSmUKs5s3I_YwfUN39p3ZyfLP4eoN7Wx5H-1q3Xpq5WKKWE_vTm2r-lHci7OuD1nPwGXbNVw</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Park, Jung-Eun</creator><creator>Kim, Hyun Tae</creator><creator>Lee, Sujin</creator><creator>Lee, Ye-Suk</creator><creator>Choi, Ung-Kyu</creator><creator>Kang, Jeong Han</creator><creator>Choi, Soo Young</creator><creator>Kang, Tae-Cheon</creator><creator>Choi, Myung-Sook</creator><creator>Kwon, Oh-Shin</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley-VCH</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20110701</creationdate><title>Differential expression of intermediate filaments in the process of developing hepatic steatosis</title><author>Park, Jung-Eun ; Kim, Hyun Tae ; Lee, Sujin ; Lee, Ye-Suk ; Choi, Ung-Kyu ; Kang, Jeong Han ; Choi, Soo Young ; Kang, Tae-Cheon ; Choi, Myung-Sook ; Kwon, Oh-Shin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6034-c3dd56683f090f652bc492b5b786c5fb367726c85dc166bc9e55aea6102db1703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animal proteomics</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Body weight</topic><topic>Cytokeratin</topic><topic>Cytoskeleton</topic><topic>Diet</topic><topic>Dietary Fats</topic><topic>Fatty acids</topic><topic>Fatty liver</topic><topic>Fatty Liver - metabolism</topic><topic>Fatty Liver - physiopathology</topic><topic>Fatty liver disease</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Profiling</topic><topic>Hepatocytes</topic><topic>Hepatocytes - chemistry</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - metabolism</topic><topic>High fat diet</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Intermediate filament</topic><topic>Intermediate filaments</topic><topic>Intermediate Filaments - metabolism</topic><topic>Keratins - genetics</topic><topic>Keratins - metabolism</topic><topic>Lipid Metabolism</topic><topic>Liver - chemistry</topic><topic>Liver - cytology</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver diseases</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Mass Spectrometry - methods</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microarray Analysis</topic><topic>Microfilaments</topic><topic>Miscellaneous</topic><topic>Obesity</topic><topic>Obesity - physiopathology</topic><topic>Other diseases. Semiology</topic><topic>Proteins</topic><topic>Proteome - analysis</topic><topic>proteomics</topic><topic>Proteomics - methods</topic><topic>Random Allocation</topic><topic>steatosis</topic><topic>Triglycerides</topic><topic>Two-Dimensional Difference Gel Electrophoresis - methods</topic><topic>Vimentin</topic><topic>Vimentin - genetics</topic><topic>Vimentin - metabolism</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Jung-Eun</creatorcontrib><creatorcontrib>Kim, Hyun Tae</creatorcontrib><creatorcontrib>Lee, Sujin</creatorcontrib><creatorcontrib>Lee, Ye-Suk</creatorcontrib><creatorcontrib>Choi, Ung-Kyu</creatorcontrib><creatorcontrib>Kang, Jeong Han</creatorcontrib><creatorcontrib>Choi, Soo Young</creatorcontrib><creatorcontrib>Kang, Tae-Cheon</creatorcontrib><creatorcontrib>Choi, Myung-Sook</creatorcontrib><creatorcontrib>Kwon, Oh-Shin</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Proteomics (Weinheim)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Jung-Eun</au><au>Kim, Hyun Tae</au><au>Lee, Sujin</au><au>Lee, Ye-Suk</au><au>Choi, Ung-Kyu</au><au>Kang, Jeong Han</au><au>Choi, Soo Young</au><au>Kang, Tae-Cheon</au><au>Choi, Myung-Sook</au><au>Kwon, Oh-Shin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential expression of intermediate filaments in the process of developing hepatic steatosis</atitle><jtitle>Proteomics (Weinheim)</jtitle><addtitle>Proteomics</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>11</volume><issue>14</issue><spage>2777</spage><epage>2789</epage><pages>2777-2789</pages><issn>1615-9853</issn><issn>1615-9861</issn><issn>1862-8346</issn><eissn>1615-9861</eissn><abstract>Obesity causes changes in fatty acid metabolism that consequently leads to fatty liver. To identify the possible proteins involved in the processes of obesity, we performed a proteomic analysis of obesity‐induced mouse liver. Male C57BL/6J mice that were fed a high‐fat diet (HFD) for 24 wk, developed hepatic steatosis characterized by considerable increase in free fatty acid (FFA) and triglyceride levels. Body weights were measured weekly and other measurements at weeks 2, 6, 12, 16, and 24. 2‐D‐based proteomic analysis revealed that, compared with the normal diet (ND) (n=50), high‐fat diet (n=50) changed the expression of 12 protein (8 up and 4 downregulated, by a 1.5× fold change and more, p&lt;0.05). The most pronounced difference was observed in intermediate microfilament (IF) cytoskeleton proteins. In particular, vimentin (vim) as well as cytokeratins (CK‐8 and CK‐18) were significantly upregulated in obese animals. Moreover, the level of caspase‐generated IF fragment was also positively correlated with the degree of steatosis. The results suggest a significant alteration in IF organization during the development of hepatic steatosis leading to inflammation. The expression profile of selected proteins including vim was validated by Western blot, microarray analysis, and hepatocyte morphology by immunohistochemistry. Our results suggest that vim, like CK‐18, may be a useful marker for predicting obesity and liver disease.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>21674798</pmid><doi>10.1002/pmic.201000544</doi><tpages>13</tpages></addata></record>
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subjects Analytical, structural and metabolic biochemistry
Animal proteomics
Animals
Biological and medical sciences
Body weight
Cytokeratin
Cytoskeleton
Diet
Dietary Fats
Fatty acids
Fatty liver
Fatty Liver - metabolism
Fatty Liver - physiopathology
Fatty liver disease
Fundamental and applied biological sciences. Psychology
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Profiling
Hepatocytes
Hepatocytes - chemistry
Hepatocytes - cytology
Hepatocytes - metabolism
High fat diet
Humans
Immunohistochemistry
Inflammation
Intermediate filament
Intermediate filaments
Intermediate Filaments - metabolism
Keratins - genetics
Keratins - metabolism
Lipid Metabolism
Liver - chemistry
Liver - cytology
Liver - metabolism
Liver - pathology
Liver diseases
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Mass Spectrometry - methods
Medical sciences
Metabolic diseases
Metabolism
Mice
Mice, Inbred C57BL
Microarray Analysis
Microfilaments
Miscellaneous
Obesity
Obesity - physiopathology
Other diseases. Semiology
Proteins
Proteome - analysis
proteomics
Proteomics - methods
Random Allocation
steatosis
Triglycerides
Two-Dimensional Difference Gel Electrophoresis - methods
Vimentin
Vimentin - genetics
Vimentin - metabolism
Western blotting
title Differential expression of intermediate filaments in the process of developing hepatic steatosis
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