Diabetes
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Impaired mitochondrial biogenesis in adipose tissue in acquired obesity Running title: Impaired mitochondrial function in obesity Sini Heinonen1#, Jana Buzkova2#, Maheswary Muniandy1, Risto Kaksonen1,3, Miina Ollikainen4, Khadeeja Ismail4,Antti Hakkarainen5, Jesse Lundbom5,6, Nina Lundbom5, Katriina Vuolteenaho7, Eeva Moilanen7, Jaakko Kaprio8,9,10, Aila Rissanen1,11, Anu Suomalainen2,12, Kirsi H. Pietiläinen1,8,13 1
Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki,
Helsinki, Finland 00014, 2Research Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland 00290, 3Siluetti Hospital, Helsinki, Finland, 4Department of Public Health, University of Helsinki, Helsinki, Finland 00014,5Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland 00014, 6Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany, 7The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland 33520, 8FIMM, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland 00014, 9Finnish Twin Cohort Study, Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki Finland 00014, 10
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland 00271, 11Department of Psychiatry and 12Neurology, , Helsinki
University Central Hospital, Helsinki, Finland, 13Abdominal Center, Endocrinology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00290. #Shared first authorship Corresponding author: Kirsi H. Pietiläinen, MD, PhD Obesity Research Unit, Biomedicum Helsinki, C424b Po Box 700 00029 Helsinki University Central Hospital Phone: +358 9 47171876, Fax: +358 50 5992295, E-mail:
[email protected]
Word count: 4415 Tables and figures: 8
Diabetes Publish Ahead of Print, published online May 13, 2015
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Abstract Low mitochondrial number and activity have been suggested as underlying factors in obesity, type 2 diabetes, and metabolic syndrome. However, the stage at which mitochondrial dysfunction manifests in adipose tissue after the onset of obesity remains unknown. Here we examined subcutaneous adipose tissue (SAT) samples from healthy monozygotic twin pairs, aged 22.8 – 36.2 years, who were discordant (∆BMI >3 kg/m2, mean length of discordance 6.3 ± 0.3 years, n = 26) and concordant (∆BMI
