title: Adipocyte morphology and implications for metabolic derangements in acquired obesity.
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.
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Heinonen
authors.affiliation: Research Programs Unit, Genome-Scale Biology and Institute of Biomedicine, Biochemistry and Developmental Biology, Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Saarinen
authors.affiliation: 1] Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland [2] FIMM, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Naukkarinen
authors.affiliation: Metabolic Research Laboratory, Clinica Universidad de Navarra, & CIBERobn, Instituto de Salud Carlos III, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Metabolic Research Laboratory, Clinica Universidad de Navarra, & CIBERobn, Instituto de Salud Carlos III, Pamplona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Frühbeck
authors.affiliation: Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Hakkarainen
authors.affiliation: Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Lundbom
authors.affiliation: Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Lundbom
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Vuolteenaho
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Moilanen
authors.affiliation: Lipid Laboratory, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Arner
authors.affiliation: Research Programs Unit, Genome-Scale Biology and Institute of Biomedicine, Biochemistry and Developmental Biology, Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Hautaniemi
authors.affiliation: Research Program of Molecular Neurology and Department of Neurology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Suomalainen
authors.affiliation: 1] FIMM, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland [2] Finnish Twin Cohort Study, Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki Finland [3] National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Rissanen
authors.affiliation: 1] Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland [2] FIMM, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland [3] Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: K H
authors.initials: KH
authors.lastname: Pietiläinen
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D004734:Energy Metabolism; D005260:Female; D005387:Finland / Q000453:epidemiology; D015870:Gene Expression; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D055442:Metabolome; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D014430:Twins, Monozygotic