FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children
Background: Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through...
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ndltd-DRESDEN-oai-qucosa.de-bsz-15-qucosa-2138442016-11-23T03:30:30Z FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children Landgraf, Kathrin Scholz, Markus Kovacs, Peter Kiess, Wieland Körner, Antje Kind Jugendlicher Adipositas Body-Mass-Index Adipozyt children adolescents obesity body mass index adipocytes ddc:601 Background: Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. Aim: We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. Results: Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the children. Conclusion: One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children. Universitätsbibliothek Leipzig Universität Leipzig, Medizinische Fakultät Universität Leipzig, Medizinische Fakultät Universität Leipzig, Medizinische Fakultät Universität Leipzig, Medizinische Fakultät Public Library of Science, 2016-11-22 doc-type:article application/pdf http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-213844 urn:nbn:de:bsz:15-qucosa-213844 http://www.qucosa.de/fileadmin/data/qucosa/documents/21384/OAP-2016-163_K%C3%B6rner_journal.pone.0161739.pdf PLoS ONE 11(8): e0161739 doi:10.1371/journal.pone.0161739 eng |
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English |
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Kind Jugendlicher Adipositas Body-Mass-Index Adipozyt children adolescents obesity body mass index adipocytes ddc:601 |
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Kind Jugendlicher Adipositas Body-Mass-Index Adipozyt children adolescents obesity body mass index adipocytes ddc:601 Landgraf, Kathrin Scholz, Markus Kovacs, Peter Kiess, Wieland Körner, Antje FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children |
description |
Background: Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte
function through targeting IRX3 and IRX5 and thermogenesis regulation. Aim: We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. Results: Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the
children. Conclusion: One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children. |
author2 |
Universität Leipzig, Medizinische Fakultät |
author_facet |
Universität Leipzig, Medizinische Fakultät Landgraf, Kathrin Scholz, Markus Kovacs, Peter Kiess, Wieland Körner, Antje |
author |
Landgraf, Kathrin Scholz, Markus Kovacs, Peter Kiess, Wieland Körner, Antje |
author_sort |
Landgraf, Kathrin |
title |
FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children |
title_short |
FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children |
title_full |
FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children |
title_fullStr |
FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children |
title_full_unstemmed |
FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children |
title_sort |
fto obesity risk variants are linked to adipocyte irx3 expression and bmi of children |
publisher |
Universitätsbibliothek Leipzig |
publishDate |
2016 |
url |
http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-213844 http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-213844 http://www.qucosa.de/fileadmin/data/qucosa/documents/21384/OAP-2016-163_K%C3%B6rner_journal.pone.0161739.pdf |
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