ORIGINAL ARTICLE Leisure-time physical activity and high-risk fat: a longitudinal population-based twin study T Leskinen 1 , S Sipila ¨ 1 , M Alen 2 , S Cheng 1 , KH Pietila ¨inen 3 , J-P Usenius 4 , H Suominen 1 , V Kovanen 1 , H Kainulainen 5 , J Kaprio 6 and UM Kujala 1 1 Department of Health Sciences, University of Jyva¨skyla¨, Jyva¨skyla¨, Finland; 2 Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland; 3 Obesity Research Unit, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland; 4 Keski-Suomen Magneettikuvaus, Jyva¨skyla¨, Finland; 5 Department of Biology of Physical Activity, UniversityofJyva¨skyla¨,Jyva¨skyla¨,Finlandand 6 Department of Public Health, University of Helsinki, Helsinki, Finland Background and Objective: Exercise is thought to reduce high-risk body fat, but intervention studies are frequently limited by short follow-ups and observational studies by genetic selection. Therefore, we studied the effects of a physically inactive vs active lifestyle on high-risk (visceral, liver and intramuscular) fat in twin pairs discordant for leisure-time physical activity habits for over 30 years. Design: A longitudinal population-based twin study. Subjects: Sixteen middle-aged (50–74 years) same-sex twin pairs (seven monozygotic (MZ), nine dizygotic (DZ)) with long- term discordance for physical activity habits were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in 1975 and the same co-twin remained significantly more active during the 32-year- long follow-up. Main Outcome Measures: Magnetic resonance imaging-assessed visceral, liver and intramuscular fat. Results: In within-pair analyses carried out after the adult life-long discordance in physical activity habits, the physically inactive co-twins had 50% greater visceral fat area compared with the active co-twins (mean difference 55.5 cm 2 , 95% confidence interval (CI) 7.0–104.1, P ¼ 0.010). The liver fat score was 170% higher (13.2, 95% CI 3.5–22.8, P ¼ 0.030) and the intramuscular fat area 54% higher (4.9 cm 2 , 95% CI 1.9–7.9, P ¼ 0.002) among the inactive co-twins. All the trends were similar for MZ and DZ pairs. Peak oxygen uptake was inversely associated with visceral (r ¼0.46, P ¼ 0.012) and intramuscular fat area (r ¼0.48, P ¼ 0.028), with similar trends in intrapair difference correlations (r ¼0.57, P ¼ 0.021 and r ¼0.50, P ¼ 0.056, respectively). The intrapair difference correlation between visceral and intramuscular fat was also high (r ¼ 0.65, P ¼ 0.009). Conclusion: Regular physical activity seems to be an important factor in preventing the accumulation of high-risk fat over time, even after controlling for genetic liability and childhood environment. Therefore, the prevention and treatment of obesity should emphasize the role of regular leisure-time physical activity. International Journal of Obesity (2009) 33, 1211–1218; doi:10.1038/ijo.2009.170; published online 1 September 2009 Keywords: physical activity; body fat; twins; visceral fat; ectopic fat Introduction Some people may inherit a tendency for high body fat. 1 However, the main causes of the obesity epidemic seem to be environmental, as the genetic pool changes slowly. 2,3 Abdominal obesity in particular is now recognized as a risk factor for cardiovascular and metabolic diseases as well as death. 4,5 Trends toward higher waist circumferences are frequently reported around the world. 6–8 Visceral obesity is strongly linked to an altered metabolic profile, possibly along with the ectopic fat deposition. 9 Deposition of fat in the liver and muscle has a major role in the development of obesity-related health risks. 10 A physically active lifestyle is assumed to have a role in the prevention of obesity, although the results on the effect of physical activity on weight gain are somewhat conflicting. 11 The effect of relatively short-term exercise training in reducing total and abdominal fat is well documented by randomized controlled trials, 12–15 but less is known regard- ing the effects of long-term physical activity on different Received 2 April 2009; revised 22 June 2009; accepted 26 July 2009; published online 1 September 2009 Correspondence: Dr T Leskinen, Department of Health Sciences, University of Jyva ¨skyla ¨, PO Box 35 (VIV), FIN-40014 University of Jyva ¨skyla ¨, Finland. E-mail: tuija.h.leskinen@jyu.fi International Journal of Obesity (2009) 33, 1211–1218 & 2009 Macmillan Publishers Limited All rights reserved 0307-0565/09 $32.00 www.nature.com/ijo