Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding
Aims/hypothesis Individuals who had a low birthweight (LBW) are at an increased risk of insulin resistance and type 2 diabetes when exposed to high-fat overfeeding (HFO). We studied genome-wide mRNA expression and DNA methylation in subcutaneous adipose tissue (SAT) after 5 days of HFO and after a c...
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| Veröffentlicht in: | Diabetologia 2016-04, Vol.59 (4), p.799-812 |
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| creator | Gillberg, Linn Perfilyev, Alexander Brøns, Charlotte Thomasen, Martin Grunnet, Louise G. Volkov, Petr Rosqvist, Fredrik Iggman, David Dahlman, Ingrid Risérus, Ulf Rönn, Tina Nilsson, Emma Vaag, Allan Ling, Charlotte |
| description | Aims/hypothesis
Individuals who had a low birthweight (LBW) are at an increased risk of insulin resistance and type 2 diabetes when exposed to high-fat overfeeding (HFO). We studied genome-wide mRNA expression and DNA methylation in subcutaneous adipose tissue (SAT) after 5 days of HFO and after a control diet in 40 young men, of whom 16 had LBW.
Methods
mRNA expression was analysed using Affymetrix Human Gene 1.0 ST arrays and DNA methylation using Illumina 450K BeadChip arrays.
Results
We found differential DNA methylation at 53 sites in SAT from LBW vs normal birthweight (NBW) men (false discovery rate |
| doi_str_mv | 10.1007/s00125-015-3852-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_508141</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1770878255</sourcerecordid><originalsourceid>FETCH-LOGICAL-c695t-90eff5e59a2c2d6db5f5eb77423123d953b8b5c4d3349f765f6fba922821dc453</originalsourceid><addsrcrecordid>eNp1ksmO1DAQhiMEYnoGHoALisRlDhPwEi_h1hpWqSUugLhZsV1Oe0jHwU5o8fY4pBkhpD54KddXf9nWXxTPMHqJERKvEkKYsAphVlHJSNU8KDa4pqRCNZEPi82SrrDk3y6Ky5TuEEKU1fxxcUG4YAhjvinGrfVjSFBOPqU5L7Edkol-nMLBm1S2gy1h9B0Ma-yHsg_HUvs47Y_gu_1UHmD4g5kwTDH06XWZZyiDK_c5X7l2KsNPiA7A-qF7UjxybZ_g6Wm9Kr68e_v59kO1-_T-4-12VxnesKlqEDjHgDUtMcRyq1mOtBA1oZhQ2zCqpWamtpTWjROcOe502xAiCbamZvSqqFbddIRx1mqM_tDGXyq0Xp2OvucdKIYkrnHmd2f5fh7z0HksBVw6jXMzJQSSquYIlCaaKa45wg6sw4ZmuZuzcm_8160KsVPzrPJ9hRQZv17xMYYfM6RJHXwy0PftAGFOCi-9hCRsediL_9C7MMch_-VKUdkwnim8UiaGlCK4-xtgpBbzqNU8KptHLeZRTa55flKe9QHsfcVft2SAnB6VU0MH8Z_WZ1V_A6_v0PQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1770838956</pqid></control><display><type>article</type><title>Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Gillberg, Linn ; Perfilyev, Alexander ; Brøns, Charlotte ; Thomasen, Martin ; Grunnet, Louise G. ; Volkov, Petr ; Rosqvist, Fredrik ; Iggman, David ; Dahlman, Ingrid ; Risérus, Ulf ; Rönn, Tina ; Nilsson, Emma ; Vaag, Allan ; Ling, Charlotte</creator><creatorcontrib>Gillberg, Linn ; Perfilyev, Alexander ; Brøns, Charlotte ; Thomasen, Martin ; Grunnet, Louise G. ; Volkov, Petr ; Rosqvist, Fredrik ; Iggman, David ; Dahlman, Ingrid ; Risérus, Ulf ; Rönn, Tina ; Nilsson, Emma ; Vaag, Allan ; Ling, Charlotte</creatorcontrib><description>Aims/hypothesis
Individuals who had a low birthweight (LBW) are at an increased risk of insulin resistance and type 2 diabetes when exposed to high-fat overfeeding (HFO). We studied genome-wide mRNA expression and DNA methylation in subcutaneous adipose tissue (SAT) after 5 days of HFO and after a control diet in 40 young men, of whom 16 had LBW.
Methods
mRNA expression was analysed using Affymetrix Human Gene 1.0 ST arrays and DNA methylation using Illumina 450K BeadChip arrays.
Results
We found differential DNA methylation at 53 sites in SAT from LBW vs normal birthweight (NBW) men (false discovery rate <5%), including sites in the
FADS2
and
CPLX1
genes previously associated with type 2 diabetes. When we used reference-free cell mixture adjustments to potentially adjust for cell composition, 4,323 sites had differential methylation in LBW vs NBW men. However, no differences in SAT gene expression levels were identified between LBW and NBW men. In the combined group of all 40 participants, 3,276 genes (16.5%) were differentially expressed in SAT after HFO (false discovery rate <5%) and there was no difference between LBW men and controls. The most strongly upregulated genes were
ELOVL6
,
FADS2
and
NNAT
; in contrast,
INSR
,
IRS2
and the
SLC27A2
fatty acid transporter showed decreased expression after HFO. Interestingly,
SLC27A2
expression correlated negatively with diabetes- and obesity-related traits in a replication cohort of 142 individuals. DNA methylation at 652 CpG sites (including in
CDK5
,
IGFBP5
and
SLC2A4
) was altered in SAT after overfeeding in this and in another cohort.
Conclusions/interpretation
Young men who had a LBW exhibit epigenetic alterations in their adipose tissue that potentially influence insulin resistance and risk of type 2 diabetes. Short-term overfeeding influences gene transcription and, to some extent, DNA methylation in adipose tissue; there was no major difference in this response between LBW and control participants.</description><identifier>ISSN: 0012-186X</identifier><identifier>ISSN: 1432-0428</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-015-3852-9</identifier><identifier>PMID: 26750116</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adaptor Proteins, Vesicular Transport - genetics ; Adipose Tissue - metabolism ; Adult ; Birth weight ; Body fat ; Clinical Medicine ; Diabetes ; Diabetes Mellitus, Type 2 - genetics ; Diet ; Diet, High-Fat - adverse effects ; DNA methylation ; DNA Methylation - genetics ; Endocrinology and Diabetes ; Endokrinologi och diabetes ; Epigenetics ; Epigenomics ; Fatty Acid Desaturases - genetics ; Gene expression ; Genomes ; Health care ; High-fat overfeeding ; Human Physiology ; Humans ; Infant, Low Birth Weight - physiology ; Insulin resistance ; Internal Medicine ; Klinisk medicin ; Low birthweight ; Male ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolic disorders ; Metabolism ; Musculoskeletal system ; Nerve Tissue Proteins - genetics ; Nutrition research ; Obesity ; Transcriptome - genetics ; Type 2 diabetes ; Young Adult</subject><ispartof>Diabetologia, 2016-04, Vol.59 (4), p.799-812</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c695t-90eff5e59a2c2d6db5f5eb77423123d953b8b5c4d3349f765f6fba922821dc453</citedby><cites>FETCH-LOGICAL-c695t-90eff5e59a2c2d6db5f5eb77423123d953b8b5c4d3349f765f6fba922821dc453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-015-3852-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-015-3852-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26750116$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-282787$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/8592468$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:133123253$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Gillberg, Linn</creatorcontrib><creatorcontrib>Perfilyev, Alexander</creatorcontrib><creatorcontrib>Brøns, Charlotte</creatorcontrib><creatorcontrib>Thomasen, Martin</creatorcontrib><creatorcontrib>Grunnet, Louise G.</creatorcontrib><creatorcontrib>Volkov, Petr</creatorcontrib><creatorcontrib>Rosqvist, Fredrik</creatorcontrib><creatorcontrib>Iggman, David</creatorcontrib><creatorcontrib>Dahlman, Ingrid</creatorcontrib><creatorcontrib>Risérus, Ulf</creatorcontrib><creatorcontrib>Rönn, Tina</creatorcontrib><creatorcontrib>Nilsson, Emma</creatorcontrib><creatorcontrib>Vaag, Allan</creatorcontrib><creatorcontrib>Ling, Charlotte</creatorcontrib><title>Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
Individuals who had a low birthweight (LBW) are at an increased risk of insulin resistance and type 2 diabetes when exposed to high-fat overfeeding (HFO). We studied genome-wide mRNA expression and DNA methylation in subcutaneous adipose tissue (SAT) after 5 days of HFO and after a control diet in 40 young men, of whom 16 had LBW.
Methods
mRNA expression was analysed using Affymetrix Human Gene 1.0 ST arrays and DNA methylation using Illumina 450K BeadChip arrays.
Results
We found differential DNA methylation at 53 sites in SAT from LBW vs normal birthweight (NBW) men (false discovery rate <5%), including sites in the
FADS2
and
CPLX1
genes previously associated with type 2 diabetes. When we used reference-free cell mixture adjustments to potentially adjust for cell composition, 4,323 sites had differential methylation in LBW vs NBW men. However, no differences in SAT gene expression levels were identified between LBW and NBW men. In the combined group of all 40 participants, 3,276 genes (16.5%) were differentially expressed in SAT after HFO (false discovery rate <5%) and there was no difference between LBW men and controls. The most strongly upregulated genes were
ELOVL6
,
FADS2
and
NNAT
; in contrast,
INSR
,
IRS2
and the
SLC27A2
fatty acid transporter showed decreased expression after HFO. Interestingly,
SLC27A2
expression correlated negatively with diabetes- and obesity-related traits in a replication cohort of 142 individuals. DNA methylation at 652 CpG sites (including in
CDK5
,
IGFBP5
and
SLC2A4
) was altered in SAT after overfeeding in this and in another cohort.
Conclusions/interpretation
Young men who had a LBW exhibit epigenetic alterations in their adipose tissue that potentially influence insulin resistance and risk of type 2 diabetes. Short-term overfeeding influences gene transcription and, to some extent, DNA methylation in adipose tissue; there was no major difference in this response between LBW and control participants.</description><subject>Adaptor Proteins, Vesicular Transport - genetics</subject><subject>Adipose Tissue - metabolism</subject><subject>Adult</subject><subject>Birth weight</subject><subject>Body fat</subject><subject>Clinical Medicine</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diet</subject><subject>Diet, High-Fat - adverse effects</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Endocrinology and Diabetes</subject><subject>Endokrinologi och diabetes</subject><subject>Epigenetics</subject><subject>Epigenomics</subject><subject>Fatty Acid Desaturases - genetics</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Health care</subject><subject>High-fat overfeeding</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Infant, Low Birth Weight - physiology</subject><subject>Insulin resistance</subject><subject>Internal Medicine</subject><subject>Klinisk medicin</subject><subject>Low birthweight</subject><subject>Male</subject><subject>Medical and Health Sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolic disorders</subject><subject>Metabolism</subject><subject>Musculoskeletal system</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nutrition research</subject><subject>Obesity</subject><subject>Transcriptome - genetics</subject><subject>Type 2 diabetes</subject><subject>Young Adult</subject><issn>0012-186X</issn><issn>1432-0428</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1ksmO1DAQhiMEYnoGHoALisRlDhPwEi_h1hpWqSUugLhZsV1Oe0jHwU5o8fY4pBkhpD54KddXf9nWXxTPMHqJERKvEkKYsAphVlHJSNU8KDa4pqRCNZEPi82SrrDk3y6Ky5TuEEKU1fxxcUG4YAhjvinGrfVjSFBOPqU5L7Edkol-nMLBm1S2gy1h9B0Ma-yHsg_HUvs47Y_gu_1UHmD4g5kwTDH06XWZZyiDK_c5X7l2KsNPiA7A-qF7UjxybZ_g6Wm9Kr68e_v59kO1-_T-4-12VxnesKlqEDjHgDUtMcRyq1mOtBA1oZhQ2zCqpWamtpTWjROcOe502xAiCbamZvSqqFbddIRx1mqM_tDGXyq0Xp2OvucdKIYkrnHmd2f5fh7z0HksBVw6jXMzJQSSquYIlCaaKa45wg6sw4ZmuZuzcm_8160KsVPzrPJ9hRQZv17xMYYfM6RJHXwy0PftAGFOCi-9hCRsediL_9C7MMch_-VKUdkwnim8UiaGlCK4-xtgpBbzqNU8KptHLeZRTa55flKe9QHsfcVft2SAnB6VU0MH8Z_WZ1V_A6_v0PQ</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Gillberg, Linn</creator><creator>Perfilyev, Alexander</creator><creator>Brøns, Charlotte</creator><creator>Thomasen, Martin</creator><creator>Grunnet, Louise G.</creator><creator>Volkov, Petr</creator><creator>Rosqvist, Fredrik</creator><creator>Iggman, David</creator><creator>Dahlman, Ingrid</creator><creator>Risérus, Ulf</creator><creator>Rönn, Tina</creator><creator>Nilsson, Emma</creator><creator>Vaag, Allan</creator><creator>Ling, Charlotte</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DF2</scope><scope>D95</scope></search><sort><creationdate>20160401</creationdate><title>Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding</title><author>Gillberg, Linn ; Perfilyev, Alexander ; Brøns, Charlotte ; Thomasen, Martin ; Grunnet, Louise G. ; Volkov, Petr ; Rosqvist, Fredrik ; Iggman, David ; Dahlman, Ingrid ; Risérus, Ulf ; Rönn, Tina ; Nilsson, Emma ; Vaag, Allan ; Ling, Charlotte</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c695t-90eff5e59a2c2d6db5f5eb77423123d953b8b5c4d3349f765f6fba922821dc453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adaptor Proteins, Vesicular Transport - genetics</topic><topic>Adipose Tissue - metabolism</topic><topic>Adult</topic><topic>Birth weight</topic><topic>Body fat</topic><topic>Clinical Medicine</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diet</topic><topic>Diet, High-Fat - adverse effects</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Endocrinology and Diabetes</topic><topic>Endokrinologi och diabetes</topic><topic>Epigenetics</topic><topic>Epigenomics</topic><topic>Fatty Acid Desaturases - genetics</topic><topic>Gene expression</topic><topic>Genomes</topic><topic>Health care</topic><topic>High-fat overfeeding</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Infant, Low Birth Weight - physiology</topic><topic>Insulin resistance</topic><topic>Internal Medicine</topic><topic>Klinisk medicin</topic><topic>Low birthweight</topic><topic>Male</topic><topic>Medical and Health Sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Metabolic disorders</topic><topic>Metabolism</topic><topic>Musculoskeletal system</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nutrition research</topic><topic>Obesity</topic><topic>Transcriptome - genetics</topic><topic>Type 2 diabetes</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gillberg, Linn</creatorcontrib><creatorcontrib>Perfilyev, Alexander</creatorcontrib><creatorcontrib>Brøns, Charlotte</creatorcontrib><creatorcontrib>Thomasen, Martin</creatorcontrib><creatorcontrib>Grunnet, Louise G.</creatorcontrib><creatorcontrib>Volkov, Petr</creatorcontrib><creatorcontrib>Rosqvist, Fredrik</creatorcontrib><creatorcontrib>Iggman, David</creatorcontrib><creatorcontrib>Dahlman, Ingrid</creatorcontrib><creatorcontrib>Risérus, Ulf</creatorcontrib><creatorcontrib>Rönn, Tina</creatorcontrib><creatorcontrib>Nilsson, Emma</creatorcontrib><creatorcontrib>Vaag, Allan</creatorcontrib><creatorcontrib>Ling, Charlotte</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Uppsala universitet</collection><collection>SWEPUB Lunds universitet</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gillberg, Linn</au><au>Perfilyev, Alexander</au><au>Brøns, Charlotte</au><au>Thomasen, Martin</au><au>Grunnet, Louise G.</au><au>Volkov, Petr</au><au>Rosqvist, Fredrik</au><au>Iggman, David</au><au>Dahlman, Ingrid</au><au>Risérus, Ulf</au><au>Rönn, Tina</au><au>Nilsson, Emma</au><au>Vaag, Allan</au><au>Ling, Charlotte</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>59</volume><issue>4</issue><spage>799</spage><epage>812</epage><pages>799-812</pages><issn>0012-186X</issn><issn>1432-0428</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
Individuals who had a low birthweight (LBW) are at an increased risk of insulin resistance and type 2 diabetes when exposed to high-fat overfeeding (HFO). We studied genome-wide mRNA expression and DNA methylation in subcutaneous adipose tissue (SAT) after 5 days of HFO and after a control diet in 40 young men, of whom 16 had LBW.
Methods
mRNA expression was analysed using Affymetrix Human Gene 1.0 ST arrays and DNA methylation using Illumina 450K BeadChip arrays.
Results
We found differential DNA methylation at 53 sites in SAT from LBW vs normal birthweight (NBW) men (false discovery rate <5%), including sites in the
FADS2
and
CPLX1
genes previously associated with type 2 diabetes. When we used reference-free cell mixture adjustments to potentially adjust for cell composition, 4,323 sites had differential methylation in LBW vs NBW men. However, no differences in SAT gene expression levels were identified between LBW and NBW men. In the combined group of all 40 participants, 3,276 genes (16.5%) were differentially expressed in SAT after HFO (false discovery rate <5%) and there was no difference between LBW men and controls. The most strongly upregulated genes were
ELOVL6
,
FADS2
and
NNAT
; in contrast,
INSR
,
IRS2
and the
SLC27A2
fatty acid transporter showed decreased expression after HFO. Interestingly,
SLC27A2
expression correlated negatively with diabetes- and obesity-related traits in a replication cohort of 142 individuals. DNA methylation at 652 CpG sites (including in
CDK5
,
IGFBP5
and
SLC2A4
) was altered in SAT after overfeeding in this and in another cohort.
Conclusions/interpretation
Young men who had a LBW exhibit epigenetic alterations in their adipose tissue that potentially influence insulin resistance and risk of type 2 diabetes. Short-term overfeeding influences gene transcription and, to some extent, DNA methylation in adipose tissue; there was no major difference in this response between LBW and control participants.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26750116</pmid><doi>10.1007/s00125-015-3852-9</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Diabetologia, 2016-04, Vol.59 (4), p.799-812 |
| issn | 0012-186X 1432-0428 1432-0428 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_508141 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adaptor Proteins, Vesicular Transport - genetics Adipose Tissue - metabolism Adult Birth weight Body fat Clinical Medicine Diabetes Diabetes Mellitus, Type 2 - genetics Diet Diet, High-Fat - adverse effects DNA methylation DNA Methylation - genetics Endocrinology and Diabetes Endokrinologi och diabetes Epigenetics Epigenomics Fatty Acid Desaturases - genetics Gene expression Genomes Health care High-fat overfeeding Human Physiology Humans Infant, Low Birth Weight - physiology Insulin resistance Internal Medicine Klinisk medicin Low birthweight Male Medical and Health Sciences Medicin och hälsovetenskap Medicine Medicine & Public Health Metabolic Diseases Metabolic disorders Metabolism Musculoskeletal system Nerve Tissue Proteins - genetics Nutrition research Obesity Transcriptome - genetics Type 2 diabetes Young Adult |
| title | Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding |
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