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Characterising metabolically healthy obesity in weight-discordant monozygotic twins
Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Biomedicum Helsinki, Finland; FIMM, Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Biomedicum Helsinki, Finland.
Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
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2014 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no 1, p. 167-176Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this ‘metabolically healthy obesity’ (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon.

Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (∆) in BMI ≥3 kg/m2), aged 22.8–35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT.

Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (∆weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (∆718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (∆weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (∆8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics.

Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO.

Place, publisher, year, edition, pages
New York, USA: Springer, 2014. Vol. 57, no 1, p. 167-176
Keywords [en]
Adipose tissue, Diabetes, Fatty liver, Inflammation, Metabolically healthy obesity, Obesity
National Category
Medical and Health Sciences Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-65686DOI: 10.1007/s00125-013-3066-yISI: 000328332900020PubMedID: 24100782Scopus ID: 2-s2.0-84890898823OAI: oai:DiVA.org:oru-65686DiVA, id: diva2:1189773
Funder
Novo NordiskAcademy of Finland, 44069, 205585, 118555EU, FP7, Seventh Framework Programme, FP7-KBBE-22270, FP7-HEALTH-F4-2007-201413
Note

Cited By :56; Export Date: 12 March 2018; Article

Funding Agencies:

Helsinki University Central Hospital

Biomedicum Helsinki

Jalmari and Rauha Ahokas (KHP)

Finnish Medical Foundations 

Finnish Foundation for Cardiovascular Research 

Competitive Research Funding of the Pirkanmaa Hospital District

Academy of Finland Centre of Excellence in Complex Disease Genetics

National Institute of Alcohol Abuse and Alcoholism 

Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2018-06-26Bibliographically approved

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Hyötyläinen, TuuliaOresic, Matej

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