Cell Reports Medicine (Apr 2021)
Molecular pathways behind acquired obesity: Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI
- Birgitta W. van der Kolk,
- Sina Saari,
- Alen Lovric,
- Muhammad Arif,
- Marcus Alvarez,
- Arthur Ko,
- Zong Miao,
- Navid Sahebekhtiari,
- Maheswary Muniandy,
- Sini Heinonen,
- Ali Oghabian,
- Riikka Jokinen,
- Sakari Jukarainen,
- Antti Hakkarainen,
- Jesper Lundbom,
- Juho Kuula,
- Per-Henrik Groop,
- Taru Tukiainen,
- Nina Lundbom,
- Aila Rissanen,
- Jaakko Kaprio,
- Evan G. Williams,
- Nicola Zamboni,
- Adil Mardinoglu,
- Päivi Pajukanta,
- Kirsi H. Pietiläinen
Affiliations
- Birgitta W. van der Kolk
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Corresponding author
- Sina Saari
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Alen Lovric
- Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet and Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
- Muhammad Arif
- Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden
- Marcus Alvarez
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Arthur Ko
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Zong Miao
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA
- Navid Sahebekhtiari
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Maheswary Muniandy
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Sini Heinonen
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Ali Oghabian
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Riikka Jokinen
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Sakari Jukarainen
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland
- Antti Hakkarainen
- HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Jesper Lundbom
- HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
- Juho Kuula
- HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Public Health Promotion Unit, National Institute for Health and Welfare, Helsinki, Finland
- Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Taru Tukiainen
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland
- Nina Lundbom
- HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Aila Rissanen
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Jaakko Kaprio
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland
- Evan G. Williams
- Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
- Nicola Zamboni
- Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
- Adil Mardinoglu
- Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; Centre for Host-Microbiome Interactions, Dental Institute, King’s College London, London, UK
- Päivi Pajukanta
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA; Institute for Precision Health, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Kirsi H. Pietiläinen
- Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Obesity Center, Abdominal Center, Helsinki University Hospital, Helsinki, Finland; Corresponding author
- Journal volume & issue
-
Vol. 2,
no. 4
p. 100226
Abstract
Summary: Tissue-specific mechanisms prompting obesity-related development complications in humans remain unclear. We apply multiomics analyses of subcutaneous adipose tissue and skeletal muscle to examine the effects of acquired obesity among 49 BMI-discordant monozygotic twin pairs. Overall, adipose tissue appears to be more affected by excess body weight than skeletal muscle. In heavier co-twins, we observe a transcriptional pattern of downregulated mitochondrial pathways in both tissues and upregulated inflammatory pathways in adipose tissue. In adipose tissue, heavier co-twins exhibit lower creatine levels; in skeletal muscle, glycolysis- and redox stress-related protein and metabolite levels remain higher. Furthermore, metabolomics analyses in both tissues reveal that several proinflammatory lipids are higher and six of the same lipid derivatives are lower in acquired obesity. Finally, in adipose tissue, but not in skeletal muscle, mitochondrial downregulation and upregulated inflammation are associated with a fatty liver, insulin resistance, and dyslipidemia, suggesting that adipose tissue dominates in acquired obesity.
