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Integrative Biology

Adipocyte morphology and implications for metabolic derangements in acquired obesity

International Journal of Obesity volume 38, pages 1423–1431 (2014)Cite this article

Subjects

Abstract

Background:

Adipocyte size and number have been suggested to predict the development of metabolic complications in obesity. However, the genetic and environmental determinants behind this phenomenon remain unclear.

Methods:

We studied this question in rare-weight discordant (intra-pair difference (Δ) body mass index (BMI) 3–10 kg m−2, n=15) and concordant (ΔBMI 0–2 kg m−2, n=5) young adult (22–35 years) monozygotic twin pairs identified from 10 birth cohorts of Finnish twins (n=5 500 pairs). Subcutaneous abdominal adipocyte size from surgical biopsies was measured under a light microscope. Adipocyte number was calculated from cell size and total body fat (D × A).

Results:

The concordant pairs were remarkably similar for adipocyte size and number (intra-class correlations 0.91–0.92, P<0.01), suggesting a strong genetic control of these measures. In the discordant pairs, the obese co-twins (BMI 30.6±0.9 kg m−2) had significantly larger adipocytes (volume 547±59 pl), than the lean co-twins (24.9±0.9 kg m−2; 356±34 pl, P<0.001). In 8/15 pairs, the obese co-twins had less adipocytes than their co-twins. These hypoplastic obese twins had significantly higher liver fat (spectroscopy), homeostatic model assessment-index, C-reactive protein and low-density lipoprotein cholesterol than their lean co-twins. Hyperplastic obesity was observed in the rest (7/15) of the pairs, obese and lean co-twins having similar metabolic measures. In all pairs, Δadipocyte volume correlated positively and Δcell number correlated negatively with Δhomeostatic model assessment-index and Δlow-density lipoprotein, independent of Δbody fat. Transcripts most significantly correlating with Δadipocyte volume were related to a reduced mitochondrial function, membrane modifications, to DNA damage and cell death.

Conclusions:

Together, hypertrophy and hypoplasia in acquired obesity are related to metabolic dysfunction, possibly through disturbances in mitochondrial function and increased cell death within the adipose tissue.

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Acknowledgements

The study was supported by Helsinki University Hospital Research Funds and grants from Novo Nordisk Foundation, Diabetes Research Foundation, Jalmari and Rauha Ahokas Foundation and Finnish Foundation for Cardiovascular Research. The study was supported by the Academy of Finland (grants 141054, 265240, 266286 and 263278). We thank the participants for their invaluable contributions to the study. Markku Turunen (MD) and Linda Mustelin(MD) are acknowledged for their help in the collection of the data.

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Authors and Affiliations

  1. Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland

    S Heinonen, J Naukkarinen & K H Pietiläinen

  2. Research Programs Unit, Genome-Scale Biology and Institute of Biomedicine, Biochemistry and Developmental Biology, Helsinki, Finland

    L Saarinen & S Hautaniemi

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

    J Naukkarinen, J Kaprio & K H Pietiläinen

  4. Metabolic Research Laboratory, Clinica Universidad de Navarra, & CIBERobn, Instituto de Salud Carlos III, Pamplona, Spain

    A Rodríguez & G Frühbeck

  5. Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland

    A Hakkarainen, J Lundbom & N Lundbom

  6. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland

    K Vuolteenaho & E Moilanen

  7. Department of Medicine, Lipid Laboratory, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

    P Arner

  8. Research Program of Molecular Neurology and Department of Neurology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

    A Suomalainen

  9. Department of Public Health, Finnish Twin Cohort Study, Hjelt Institute, University of Helsinki, Helsinki, Finland

    J Kaprio

  10. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland

    J Kaprio

  11. Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland

    A Rissanen

  12. Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland

    K H Pietiläinen

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  1. S Heinonen
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Correspondence to K H Pietiläinen.

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Heinonen, S., Saarinen, L., Naukkarinen, J. et al. Adipocyte morphology and implications for metabolic derangements in acquired obesity. Int J Obes 38, 1423–1431 (2014). https://doi.org/10.1038/ijo.2014.31

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