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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/E148    most recent 00580.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mustelin, L. Articles by Yki-Järvinen, H. PubMed PubMed Citation Articles by Mustelin, L. Articles by Yki-Järvinen, H.

Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity

¹Department of Laboratory Medicine, Division of Clinical Physiology and Nuclear Medicine; Helsinki University Central Hospital; ²Finnish Twin Cohort Study, Department of Public Health, University of Helsinki; ³Obesity Research Unit, Department of Psychiatry; Helsinki University Central Hospital; ⁴Department of Medicine, Division of Diabetes, Helsinki University Central Hospital; ⁵Department of Molecular Medicine, National Public Health Institute, Helsinki, and Department of Medical Genetics and Research Program of Molecular Medicine, University of Helsinki; ⁶Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki; and ⁷Minerva Medical Research Institute, Helsinki, Finland

Submitted 7 September 2007 ; accepted in final form 22 April 2008

Defects in expression of genes of oxidative phosphorylation in mitochondria have been suggested to be a key pathophysiological feature in familial insulin resistance. We examined whether such defects can arise from lifestyle-related factors alone. Fourteen obesity-discordant (BMI difference 5.2 ± 1.8 kg/m²) and 10 concordant (1.0 ± 0.7 kg/m²) monozygotic (MZ) twin pairs aged 24–27 yr were identified among 658 MZ pairs in the population-based FinnTwin16 study. Whole body insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp technique. Transcript profiles of mitochondrial genes were compared using microarray data of fat biopsies from discordant twins. Body composition of twins was determined using DEXA and maximal oxygen uptake (O_2max) and working capacity (W_max) using a bicycle ergometer exercise test with gas exchange analysis. The obese cotwins had lower insulin sensitivity than their nonobese counterparts (M value 6.1 ± 2.0 vs. 9.2 ± 3.2 mg·kg LBM^–1·min^–1, P < 0.01). Transcript levels of genes involved in the oxidative phosphorylation pathway (GO:0006119) in adipose tissue were lower (P < 0.05) in the obese compared with the nonobese cotwins. The obese cotwins were also less fit, as measured by O_2max (50.6 ± 6.5 vs. 54.2 ± 6.4 ml·kg LBM^–1·min^–1, for obese vs. nonobese, P < 0.05), W_max (3.9 ± 0.5 vs. 4.4 ± 0.7 W/kg LBM, P < 0.01) and also less active, by the Baecke leisure time physical activity index (2.8 ± 0.5 vs. 3.3 ± 0.6, P < 0.01). This implies that acquired poor physical fitness is associated with defective expression of the oxidative pathway components in adipose tissue mitochondria.

body composition; cardiorespiratory fitness; spiroergometry; gene expression