PLoS Medicine (Mar 2008)

Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity.

  • 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

DOI
https://doi.org/10.1371/journal.pmed.0050051
Journal volume & issue
Vol. 5, no. 3
p. e51

Abstract

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BackgroundThe 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.Methods and findingsWe 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 ConclusionsOur findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance.