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Molecular pathways behind acquired obesity: Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI.
van der Kolk, Birgitta W; Saari, Sina; Lovric, Alen; Arif, Muhammad; Alvarez, Marcus; Ko, Arthur; Miao, Zong; Sahebekhtiari, Navid; Muniandy, Maheswary; Heinonen, Sini; Oghabian, Ali; Jokinen, Riikka; Jukarainen, Sakari; Hakkarainen, Antti; Lundbom, Jesper; Kuula, Juho; Groop, Per-Henrik; Tukiainen, Taru; Lundbom, Nina; Rissanen, Aila; Kaprio, Jaakko; Williams, Evan G; Zamboni, Nicola; Mardinoglu, Adil; Pajukanta, Päivi; Pietiläinen, Kirsi H.
Affiliation
  • van der Kolk BW; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Saari S; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Lovric A; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
  • Arif M; Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet and Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden.
  • Alvarez M; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
  • Ko A; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Miao Z; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Sahebekhtiari N; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Muniandy M; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA.
  • Heinonen S; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Oghabian A; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Jokinen R; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Jukarainen S; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Hakkarainen A; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Lundbom J; Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland.
  • Kuula J; HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • Groop PH; HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • Tukiainen T; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.
  • Lundbom N; HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • Rissanen A; Public Health Promotion Unit, National Institute for Health and Welfare, Helsinki, Finland.
  • Kaprio J; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
  • Williams EG; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Zamboni N; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • Mardinoglu A; Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.
  • Pajukanta P; Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland.
  • Pietiläinen KH; HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Cell Rep Med ; 2(4): 100226, 2021 04 20.
Article in En | MEDLINE | ID: mdl-33948567
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Body Mass Index / Adipose Tissue / Muscle, Skeletal / Obesity Language: En Journal: Cell Rep Med Year: 2021 Type: Article Affiliation country: Finland
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Body Mass Index / Adipose Tissue / Muscle, Skeletal / Obesity Language: En Journal: Cell Rep Med Year: 2021 Type: Article Affiliation country: Finland