An Epigenetic Signature in Adipose Tissue Is Linked to Nicotinamide N‐Methyltransferase Gene Expression
Scope The enzyme nicotinamide N‐methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue. Methods and results The global human methylome was analyzed in visceral adipose tissue (VAT) fr...
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| Veröffentlicht in: | Molecular nutrition & food research 2018-07, Vol.62 (14), p.e1700933-n/a |
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| creator | Crujeiras, Ana B. Pissios, Pavlos Moreno‐Navarrete, Jose M. Diaz‐Lagares, Angel Sandoval, Juan Gomez, Antonio Ricart, Wilfredo Esteller, Manel Casanueva, Felipe F. Fernandez‐Real, Jose M. |
| description | Scope
The enzyme nicotinamide N‐methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue.
Methods and results
The global human methylome was analyzed in visceral adipose tissue (VAT) from morbidly obese patients using the Infinium Human Methylation 450 BeadChip array (discovery cohort: n = 11). The findings were confirmed in two additional independent cohorts (cohort 1: n = 60; BMI 20–60 kg m−2 and cohort 2: n = 40; BMI > 40 kg m−2) and validated after weight loss (using microarray data). Among the genes associated with the largest methylation fold change were genes related to metabolic processes, proliferation, inflammation, and extracellular matrix remodeling, such as COL23A1, PLEC1, FBXO21, STEAP3, RGS12, IGDCC3, FOXK2, and ORAI2. In fact, the results showed 577 differentially methylated CpG sites (DMCpGs) associated with the NNMT expression levels, with low methylation levels paralleling high NNMT expression. The expression of FBXO21 and FOXK2 was specifically modified after weight loss concomitantly with a decrease in NNMT expression and inflammation‐related genes. Interestingly, the adipose tissue NNMT gene expression correlated with markers of adipose tissue inflammation.
Conclusions
The expression of NNMT in VAT is associated with a specific methylome signature involving genes linked to adipose tissue metabolic pathophysiology.
This study is the first to investigate the global methylome of VAT obtained from morbidly obese patients in association with the expression of nicotinamide N‐methyltransferase (NNMT). Higher NNMT expression is associated with lower global DNA methylation in visceral adipose tissue from morbidly obese patients. The genes mapped by the NNMT‐related DMCpG sites belong to a family of genes involved in adipose tissue pathophysiology. The expression of the differentially methylated genes changes in the expected direction after bariatric‐induced weight loss parallel to NNMT. |
| doi_str_mv | 10.1002/mnfr.201700933 |
| format | Article |
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The enzyme nicotinamide N‐methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue.
Methods and results
The global human methylome was analyzed in visceral adipose tissue (VAT) from morbidly obese patients using the Infinium Human Methylation 450 BeadChip array (discovery cohort: n = 11). The findings were confirmed in two additional independent cohorts (cohort 1: n = 60; BMI 20–60 kg m−2 and cohort 2: n = 40; BMI > 40 kg m−2) and validated after weight loss (using microarray data). Among the genes associated with the largest methylation fold change were genes related to metabolic processes, proliferation, inflammation, and extracellular matrix remodeling, such as COL23A1, PLEC1, FBXO21, STEAP3, RGS12, IGDCC3, FOXK2, and ORAI2. In fact, the results showed 577 differentially methylated CpG sites (DMCpGs) associated with the NNMT expression levels, with low methylation levels paralleling high NNMT expression. The expression of FBXO21 and FOXK2 was specifically modified after weight loss concomitantly with a decrease in NNMT expression and inflammation‐related genes. Interestingly, the adipose tissue NNMT gene expression correlated with markers of adipose tissue inflammation.
Conclusions
The expression of NNMT in VAT is associated with a specific methylome signature involving genes linked to adipose tissue metabolic pathophysiology.
This study is the first to investigate the global methylome of VAT obtained from morbidly obese patients in association with the expression of nicotinamide N‐methyltransferase (NNMT). Higher NNMT expression is associated with lower global DNA methylation in visceral adipose tissue from morbidly obese patients. The genes mapped by the NNMT‐related DMCpG sites belong to a family of genes involved in adipose tissue pathophysiology. The expression of the differentially methylated genes changes in the expected direction after bariatric‐induced weight loss parallel to NNMT.</description><identifier>ISSN: 1613-4125</identifier><identifier>EISSN: 1613-4133</identifier><identifier>DOI: 10.1002/mnfr.201700933</identifier><identifier>PMID: 29688621</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Adipose tissue ; adiposity ; biomarkers ; Body mass ; CpG islands ; DNA methylation ; DNA microarrays ; Epigenetics ; Extracellular matrix ; Gene expression ; Genes ; Inflammation ; Metabolism ; methylation ; Methyltransferase ; Nicotinamide ; obesity ; Weight loss</subject><ispartof>Molecular nutrition & food research, 2018-07, Vol.62 (14), p.e1700933-n/a</ispartof><rights>2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3683-7c52949a3bbddd6c139768fec3d664c4e75c7bb7a08c40dd7936b191bcb8a153</citedby><cites>FETCH-LOGICAL-c3683-7c52949a3bbddd6c139768fec3d664c4e75c7bb7a08c40dd7936b191bcb8a153</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%2Fmnfr.201700933$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmnfr.201700933$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29688621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Crujeiras, Ana B.</creatorcontrib><creatorcontrib>Pissios, Pavlos</creatorcontrib><creatorcontrib>Moreno‐Navarrete, Jose M.</creatorcontrib><creatorcontrib>Diaz‐Lagares, Angel</creatorcontrib><creatorcontrib>Sandoval, Juan</creatorcontrib><creatorcontrib>Gomez, Antonio</creatorcontrib><creatorcontrib>Ricart, Wilfredo</creatorcontrib><creatorcontrib>Esteller, Manel</creatorcontrib><creatorcontrib>Casanueva, Felipe F.</creatorcontrib><creatorcontrib>Fernandez‐Real, Jose M.</creatorcontrib><title>An Epigenetic Signature in Adipose Tissue Is Linked to Nicotinamide N‐Methyltransferase Gene Expression</title><title>Molecular nutrition & food research</title><addtitle>Mol Nutr Food Res</addtitle><description>Scope
The enzyme nicotinamide N‐methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue.
Methods and results
The global human methylome was analyzed in visceral adipose tissue (VAT) from morbidly obese patients using the Infinium Human Methylation 450 BeadChip array (discovery cohort: n = 11). The findings were confirmed in two additional independent cohorts (cohort 1: n = 60; BMI 20–60 kg m−2 and cohort 2: n = 40; BMI > 40 kg m−2) and validated after weight loss (using microarray data). Among the genes associated with the largest methylation fold change were genes related to metabolic processes, proliferation, inflammation, and extracellular matrix remodeling, such as COL23A1, PLEC1, FBXO21, STEAP3, RGS12, IGDCC3, FOXK2, and ORAI2. In fact, the results showed 577 differentially methylated CpG sites (DMCpGs) associated with the NNMT expression levels, with low methylation levels paralleling high NNMT expression. The expression of FBXO21 and FOXK2 was specifically modified after weight loss concomitantly with a decrease in NNMT expression and inflammation‐related genes. Interestingly, the adipose tissue NNMT gene expression correlated with markers of adipose tissue inflammation.
Conclusions
The expression of NNMT in VAT is associated with a specific methylome signature involving genes linked to adipose tissue metabolic pathophysiology.
This study is the first to investigate the global methylome of VAT obtained from morbidly obese patients in association with the expression of nicotinamide N‐methyltransferase (NNMT). Higher NNMT expression is associated with lower global DNA methylation in visceral adipose tissue from morbidly obese patients. The genes mapped by the NNMT‐related DMCpG sites belong to a family of genes involved in adipose tissue pathophysiology. The expression of the differentially methylated genes changes in the expected direction after bariatric‐induced weight loss parallel to NNMT.</description><subject>Adipose tissue</subject><subject>adiposity</subject><subject>biomarkers</subject><subject>Body mass</subject><subject>CpG islands</subject><subject>DNA methylation</subject><subject>DNA microarrays</subject><subject>Epigenetics</subject><subject>Extracellular matrix</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Inflammation</subject><subject>Metabolism</subject><subject>methylation</subject><subject>Methyltransferase</subject><subject>Nicotinamide</subject><subject>obesity</subject><subject>Weight loss</subject><issn>1613-4125</issn><issn>1613-4133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFkUFP3DAQha2qqFDaK8fKEpdedmt7Ejs5rtBCkZZFgr1Hjj0B08QJdqJ2b_0J_EZ-CUYLe-il0kgzh-89jd4j5ISzOWdM_Oh8E-aCccVYCfCBHHHJYZZxgI_7W-SH5HOMD4wBFxl8IoeilEUhBT8ibuHpcnB36HF0ht66O6_HKSB1ni6sG_qIdONinJBeRrpy_hdaOvZ07Uw_Oq87Z5Gun_8-XeF4v23HoH1sMOgku0iedPlnCBij6_0XctDoNuLXt31MNufLzdnP2er64vJssZoZkAXMlMlFmZUa6tpaKw2HUsmiQQNWysxkqHKj6lppVpiMWatKkDUveW3qQvMcjsn3ne0Q-scJ41h1LhpsW-2xn2IlUghp8kwl9PQf9KGfgk_PJUpByQsleKLmO8qEPsaATTUE1-mwrTirXjuoXjuo9h0kwbc326nu0O7x99ATkO2A367F7X_sqqv1-Q0IAfAC486TZA</recordid><startdate>201807</startdate><enddate>201807</enddate><creator>Crujeiras, Ana B.</creator><creator>Pissios, Pavlos</creator><creator>Moreno‐Navarrete, Jose M.</creator><creator>Diaz‐Lagares, Angel</creator><creator>Sandoval, Juan</creator><creator>Gomez, Antonio</creator><creator>Ricart, Wilfredo</creator><creator>Esteller, Manel</creator><creator>Casanueva, Felipe F.</creator><creator>Fernandez‐Real, Jose M.</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201807</creationdate><title>An Epigenetic Signature in Adipose Tissue Is Linked to Nicotinamide N‐Methyltransferase Gene Expression</title><author>Crujeiras, Ana B. ; Pissios, Pavlos ; Moreno‐Navarrete, Jose M. ; Diaz‐Lagares, Angel ; Sandoval, Juan ; Gomez, Antonio ; Ricart, Wilfredo ; Esteller, Manel ; Casanueva, Felipe F. ; Fernandez‐Real, Jose M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3683-7c52949a3bbddd6c139768fec3d664c4e75c7bb7a08c40dd7936b191bcb8a153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adipose tissue</topic><topic>adiposity</topic><topic>biomarkers</topic><topic>Body mass</topic><topic>CpG islands</topic><topic>DNA methylation</topic><topic>DNA microarrays</topic><topic>Epigenetics</topic><topic>Extracellular matrix</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Inflammation</topic><topic>Metabolism</topic><topic>methylation</topic><topic>Methyltransferase</topic><topic>Nicotinamide</topic><topic>obesity</topic><topic>Weight loss</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Crujeiras, Ana B.</creatorcontrib><creatorcontrib>Pissios, Pavlos</creatorcontrib><creatorcontrib>Moreno‐Navarrete, Jose M.</creatorcontrib><creatorcontrib>Diaz‐Lagares, Angel</creatorcontrib><creatorcontrib>Sandoval, Juan</creatorcontrib><creatorcontrib>Gomez, Antonio</creatorcontrib><creatorcontrib>Ricart, Wilfredo</creatorcontrib><creatorcontrib>Esteller, Manel</creatorcontrib><creatorcontrib>Casanueva, Felipe F.</creatorcontrib><creatorcontrib>Fernandez‐Real, Jose M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular nutrition & food research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crujeiras, Ana B.</au><au>Pissios, Pavlos</au><au>Moreno‐Navarrete, Jose M.</au><au>Diaz‐Lagares, Angel</au><au>Sandoval, Juan</au><au>Gomez, Antonio</au><au>Ricart, Wilfredo</au><au>Esteller, Manel</au><au>Casanueva, Felipe F.</au><au>Fernandez‐Real, Jose M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Epigenetic Signature in Adipose Tissue Is Linked to Nicotinamide N‐Methyltransferase Gene Expression</atitle><jtitle>Molecular nutrition & food research</jtitle><addtitle>Mol Nutr Food Res</addtitle><date>2018-07</date><risdate>2018</risdate><volume>62</volume><issue>14</issue><spage>e1700933</spage><epage>n/a</epage><pages>e1700933-n/a</pages><issn>1613-4125</issn><eissn>1613-4133</eissn><abstract>Scope
The enzyme nicotinamide N‐methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue.
Methods and results
The global human methylome was analyzed in visceral adipose tissue (VAT) from morbidly obese patients using the Infinium Human Methylation 450 BeadChip array (discovery cohort: n = 11). The findings were confirmed in two additional independent cohorts (cohort 1: n = 60; BMI 20–60 kg m−2 and cohort 2: n = 40; BMI > 40 kg m−2) and validated after weight loss (using microarray data). Among the genes associated with the largest methylation fold change were genes related to metabolic processes, proliferation, inflammation, and extracellular matrix remodeling, such as COL23A1, PLEC1, FBXO21, STEAP3, RGS12, IGDCC3, FOXK2, and ORAI2. In fact, the results showed 577 differentially methylated CpG sites (DMCpGs) associated with the NNMT expression levels, with low methylation levels paralleling high NNMT expression. The expression of FBXO21 and FOXK2 was specifically modified after weight loss concomitantly with a decrease in NNMT expression and inflammation‐related genes. Interestingly, the adipose tissue NNMT gene expression correlated with markers of adipose tissue inflammation.
Conclusions
The expression of NNMT in VAT is associated with a specific methylome signature involving genes linked to adipose tissue metabolic pathophysiology.
This study is the first to investigate the global methylome of VAT obtained from morbidly obese patients in association with the expression of nicotinamide N‐methyltransferase (NNMT). Higher NNMT expression is associated with lower global DNA methylation in visceral adipose tissue from morbidly obese patients. The genes mapped by the NNMT‐related DMCpG sites belong to a family of genes involved in adipose tissue pathophysiology. The expression of the differentially methylated genes changes in the expected direction after bariatric‐induced weight loss parallel to NNMT.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29688621</pmid><doi>10.1002/mnfr.201700933</doi><tpages>11</tpages></addata></record> |
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| subjects | Adipose tissue adiposity biomarkers Body mass CpG islands DNA methylation DNA microarrays Epigenetics Extracellular matrix Gene expression Genes Inflammation Metabolism methylation Methyltransferase Nicotinamide obesity Weight loss |
| title | An Epigenetic Signature in Adipose Tissue Is Linked to Nicotinamide N‐Methyltransferase Gene Expression |
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