Molecular pathways behind acquired obesity: Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI.

Adipocytes / metabolism Adipose Tissue / metabolism Body Mass Index Inflammation / metabolism Insulin Resistance / physiology Mitochondria / metabolism Muscle, Skeletal / metabolism Obesity / metabolism Subcutaneous Fat / metabolism Twins, Monozygotic / genetics
adipose tissue genome-scale metabolic models metabolomics multiomics obesity proteomics skeletal muscle transcriptomics twins

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
20 04 2021
Historique:
received: 09 10 2020
revised: 31 12 2020
accepted: 04 03 2021
entrez: 5 5 2021
pubmed: 6 5 2021
medline: 6 5 2021
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1016/j.xcrm.2021.100226 PMID: 33948567 PMC: PMC8080113
pubmed: 33948567
doi: 10.1016/j.xcrm.2021.100226
pii: S2666-3791(21)00042-2
pmc: PMC8080113
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Twin Study

Langues

eng

Pagination

100226

Subventions

Organisme : NHLBI NIH HHS
ID : P01 HL028481
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL095056
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK105561
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Informations de copyright

© 2021 The Authors.

Déclaration de conflit d'intérêts

The authors declare no competing interests.

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Auteurs

Birgitta W van der Kolk (BW)

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Sina Saari (S)

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Alen Lovric (A)

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 (M)

Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.

Marcus Alvarez (M)

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Arthur Ko (A)

Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Zong Miao (Z)

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 (N)

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Maheswary Muniandy (M)

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Sini Heinonen (S)

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Ali Oghabian (A)

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Riikka Jokinen (R)

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Sakari Jukarainen (S)

Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland.

Antti Hakkarainen (A)

HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Jesper Lundbom (J)

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 (J)

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 (PH)

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 (T)

Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland.

Nina Lundbom (N)

HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Aila Rissanen (A)

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Jaakko Kaprio (J)

Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland.

Evan G Williams (EG)

Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.

Nicola Zamboni (N)

Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.

Adil Mardinoglu (A)

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 (P)

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 (KH)

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.

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Adipocytes › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Mesures épidémiologiques › Biométrie › Anthropométrie › Indice de masse corporelle › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Insulinorésistance › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Muscles squelettiques › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux blanc › Graisse sous-cutanée › Molecular pathways behind acquired obesity:...
questionsmedicales.fr › Personnes › Progéniture de naissance multiple › Jumeaux › Jumeaux monozygotes › Molecular pathways behind acquired obesity:...