Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity.
<h4>Background</h4>The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obes...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-03-01
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| Series: | PLoS Medicine |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18336063/?tool=EBI |
| _version_ | 1818435656980889600 |
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| author | Kirsi H Pietiläinen Jussi Naukkarinen Aila Rissanen Juha Saharinen Pekka Ellonen Heli Keränen Anu Suomalainen Alexandra Götz Tapani Suortti Hannele Yki-Järvinen Matej Oresic Jaakko Kaprio Leena Peltonen |
| author_facet | Kirsi H Pietiläinen Jussi Naukkarinen Aila Rissanen Juha Saharinen Pekka Ellonen Heli Keränen Anu Suomalainen Alexandra Götz Tapani Suortti Hannele Yki-Järvinen Matej Oresic Jaakko Kaprio Leena Peltonen |
| author_sort | Kirsi H Pietiläinen |
| collection | DOAJ |
| description | <h4>Background</h4>The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obesity, a deeper understanding of the concurrent metabolic changes is of considerable importance. The goal of this study was to investigate this important acquired component and expose obesity-induced changes in biological pathways in an identical genetic background.<h4>Methods and findings</h4>We used a special study design of "clonal controls," rare monozygotic twins discordant for obesity identified through a national registry of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male, six female; white), with a mean +/- standard deviation (SD) age 25.8 +/- 1.4 y and a body mass index (BMI) difference 5.2 +/- 1.8 kg/m(2). Sequence analyses of mitochondrial DNA (mtDNA) in subcutaneous fat and peripheral leukocytes revealed no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was reduced by 47% in the obese co-twin's fat. In addition, novel pathway analyses of the adipose tissue transcription profiles exposed significant down-regulation of mitochondrial branched-chain amino acid (BCAA) catabolism (p < 0.0001). In line with this finding, serum levels of insulin secretion-enhancing BCAAs were increased in obese male co-twins (9% increase, p = 0.025). Lending clinical relevance to the findings, in both sexes the observed aberrations in mitochondrial amino acid metabolism pathways in fat correlated closely with liver fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of acquired obesity in these healthy young adults.<h4>Conclusions</h4>Our findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance. |
| first_indexed | 2024-12-14T16:56:22Z |
| format | Article |
| id | doaj.art-9c1d27490def4fc7ae999f3a5beb2ce1 |
| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-12-14T16:56:22Z |
| publishDate | 2008-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj.art-9c1d27490def4fc7ae999f3a5beb2ce12022-12-21T22:53:57ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762008-03-0153e5110.1371/journal.pmed.0050051Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity.Kirsi H PietiläinenJussi NaukkarinenAila RissanenJuha SaharinenPekka EllonenHeli KeränenAnu SuomalainenAlexandra GötzTapani SuorttiHannele Yki-JärvinenMatej OresicJaakko KaprioLeena Peltonen<h4>Background</h4>The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obesity, a deeper understanding of the concurrent metabolic changes is of considerable importance. The goal of this study was to investigate this important acquired component and expose obesity-induced changes in biological pathways in an identical genetic background.<h4>Methods and findings</h4>We used a special study design of "clonal controls," rare monozygotic twins discordant for obesity identified through a national registry of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male, six female; white), with a mean +/- standard deviation (SD) age 25.8 +/- 1.4 y and a body mass index (BMI) difference 5.2 +/- 1.8 kg/m(2). Sequence analyses of mitochondrial DNA (mtDNA) in subcutaneous fat and peripheral leukocytes revealed no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was reduced by 47% in the obese co-twin's fat. In addition, novel pathway analyses of the adipose tissue transcription profiles exposed significant down-regulation of mitochondrial branched-chain amino acid (BCAA) catabolism (p < 0.0001). In line with this finding, serum levels of insulin secretion-enhancing BCAAs were increased in obese male co-twins (9% increase, p = 0.025). Lending clinical relevance to the findings, in both sexes the observed aberrations in mitochondrial amino acid metabolism pathways in fat correlated closely with liver fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of acquired obesity in these healthy young adults.<h4>Conclusions</h4>Our findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18336063/?tool=EBI |
| spellingShingle | Kirsi H Pietiläinen Jussi Naukkarinen Aila Rissanen Juha Saharinen Pekka Ellonen Heli Keränen Anu Suomalainen Alexandra Götz Tapani Suortti Hannele Yki-Järvinen Matej Oresic Jaakko Kaprio Leena Peltonen Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. PLoS Medicine |
| title | Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. |
| title_full | Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. |
| title_fullStr | Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. |
| title_full_unstemmed | Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. |
| title_short | Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. |
| title_sort | global transcript profiles of fat in monozygotic twins discordant for bmi pathways behind acquired obesity |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18336063/?tool=EBI |
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