Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity
<p dir="ltr">Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is...
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2013
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| _version_ | 1864513510308839424 |
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| author | Mohamed Abu-Farha (18535590) |
| author2 | Ali Tiss (437068) Jehad Abubaker (18535605) Abdelkrim Khadir (437074) Fahad Al-Ghimlas (412125) Irina Al-Khairi (437069) Engin Baturcam (309036) Preethi Cherian (437070) Naser Elkum (79418) Maha Hammad (437071) Jeena John (437072) Sina Kavalakatt (437073) Samia Warsame (437075) Kazem Behbehani (412126) Said Dermime (15263545) Mohammed Dehbi (14152758) |
| author2_role | author author author author author author author author author author author author author author author |
| author_facet | Mohamed Abu-Farha (18535590) Ali Tiss (437068) Jehad Abubaker (18535605) Abdelkrim Khadir (437074) Fahad Al-Ghimlas (412125) Irina Al-Khairi (437069) Engin Baturcam (309036) Preethi Cherian (437070) Naser Elkum (79418) Maha Hammad (437071) Jeena John (437072) Sina Kavalakatt (437073) Samia Warsame (437075) Kazem Behbehani (412126) Said Dermime (15263545) Mohammed Dehbi (14152758) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mohamed Abu-Farha (18535590) Ali Tiss (437068) Jehad Abubaker (18535605) Abdelkrim Khadir (437074) Fahad Al-Ghimlas (412125) Irina Al-Khairi (437069) Engin Baturcam (309036) Preethi Cherian (437070) Naser Elkum (79418) Maha Hammad (437071) Jeena John (437072) Sina Kavalakatt (437073) Samia Warsame (437075) Kazem Behbehani (412126) Said Dermime (15263545) Mohammed Dehbi (14152758) |
| dc.date.none.fl_str_mv | 2013-09-24T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pone.0075342 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Proteomics_Analysis_of_Human_Obesity_Reveals_the_Epigenetic_Factor_HDAC4_as_a_Potential_Target_for_Obesity/26362051 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Medical physiology Chemical sciences Medicinal and biomolecular chemistry Obesity Exercise DNA-binding proteins Adipose tissue Protein expression Computer software Cytoskeletal proteins Inflammation |
| dc.title.none.fl_str_mv | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs) extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1) was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4) was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max) but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent a potential therapeutic target for the control and management of obesity and presumably insulin resistance.</p><h2>Other Information</h2><p dir="ltr">Published in: PLoS ONE<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://doi.org/10.1371/journal.pone.0075342" rel="noreferrer" target="_blank">https://doi.org/10.1371/journal.pone.0075342</a></p><p dir="ltr">Additional institutions affiliated with: Medicine and Systems Biology Research Center - QBRI</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_f596906b9acd948b7bd59dd1857aecd6 |
| identifier_str_mv | 10.1371/journal.pone.0075342 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26362051 |
| publishDate | 2013 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for ObesityMohamed Abu-Farha (18535590)Ali Tiss (437068)Jehad Abubaker (18535605)Abdelkrim Khadir (437074)Fahad Al-Ghimlas (412125)Irina Al-Khairi (437069)Engin Baturcam (309036)Preethi Cherian (437070)Naser Elkum (79418)Maha Hammad (437071)Jeena John (437072)Sina Kavalakatt (437073)Samia Warsame (437075)Kazem Behbehani (412126)Said Dermime (15263545)Mohammed Dehbi (14152758)Biomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsMedical physiologyChemical sciencesMedicinal and biomolecular chemistryObesityExerciseDNA-binding proteinsAdipose tissueProtein expressionComputer softwareCytoskeletal proteinsInflammation<p dir="ltr">Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs) extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1) was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4) was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max) but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent a potential therapeutic target for the control and management of obesity and presumably insulin resistance.</p><h2>Other Information</h2><p dir="ltr">Published in: PLoS ONE<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://doi.org/10.1371/journal.pone.0075342" rel="noreferrer" target="_blank">https://doi.org/10.1371/journal.pone.0075342</a></p><p dir="ltr">Additional institutions affiliated with: Medicine and Systems Biology Research Center - QBRI</p>2013-09-24T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1371/journal.pone.0075342https://figshare.com/articles/journal_contribution/Proteomics_Analysis_of_Human_Obesity_Reveals_the_Epigenetic_Factor_HDAC4_as_a_Potential_Target_for_Obesity/26362051CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/263620512013-09-24T06:00:00Z |
| spellingShingle | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity Mohamed Abu-Farha (18535590) Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Medical physiology Chemical sciences Medicinal and biomolecular chemistry Obesity Exercise DNA-binding proteins Adipose tissue Protein expression Computer software Cytoskeletal proteins Inflammation |
| status_str | publishedVersion |
| title | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity |
| title_full | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity |
| title_fullStr | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity |
| title_full_unstemmed | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity |
| title_short | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity |
| title_sort | Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity |
| topic | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Medical physiology Chemical sciences Medicinal and biomolecular chemistry Obesity Exercise DNA-binding proteins Adipose tissue Protein expression Computer software Cytoskeletal proteins Inflammation |