Submitted on September 7, 2007
Accepted on April 22, 2008
Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity
Linda Mustelin1*, Kirsi H Pietilainen2, Aila Rissanen3, Anssi Raimo Sovijarvi4, Paivi Piirila5, Jussi Naukkarinen6, Leena Peltonen7, Jaakko Kaprio8, and Hannele Yki-Jarvinen9
1 Department of Public Health, Twin Research Unit, University of Helsinki, Mannerheimintie 172, Helsinki, 00014, Finland; Department of Laboratory Medicine, Division of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland
2 Department of Public Health, Twin Research Unit, University of Helsinki, Mannerheimintie 172, Helsinki, 00014, Finland; Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland; Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Helsinki, Finland
3 Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
4 Department of Laboratory Medicine, Division of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland
5 Department of Laboratory Medicine, Division of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland; Helsinki, Finland
6 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
7 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland; Department of Medical Genetics and Research Program of Molecular Medicine, University of Helsinki, United States
8 Finnish Twin Cohort Study, Department of Public Health, University of Helsinki, Helsinki, Finland; Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland
9 Department of Medicine/Division of Diabetes, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland; Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland
* To whom correspondence should be addressed. E-mail: linda.mustelin{at}helsinki.fi.
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 defect 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) 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 (VO2max) and working capacity (Wmax) using a bicycle ergometer exercise test with gas exchange analysis. The obese co-twins had lower insulin sensitivity than their non-obese counterparts (M-value 6.1 ± 2.0 mg/kgLBM·min vs. 9.2 ± 3.2 mg/kgLBM·min, P<0.01). Transcript levels of genes involved in the oxidative phophorylation pathway (GO:0006119) in adipose tissue were lower (P<0.05) in the obese as compared to the non-obese co-twins. The obese co-twins were also less fit, as measured by VO2max (50.6 ± 6.5 ml/kgLBM·min vs. 54.2 ± 6.4 ml/kgLBM·min, for obese vs. non-obese, P<0.05), Wmax (3.9 ± 0.5 W/kgLBM vs. 4.4 ± 0.7 W/kgLBM, 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 would imply that acquired poor physical fitness is associated with defective expression of the oxidative pathway components in adipose tissue mitochondria.
