Adipocyte morphology and implications for metabolic derangements in acquired obesity

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 (Delta) body mass index (BMI) 3-10 kg m(-2), n = 15) and concordant (Delta BMI 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 x 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, Delta adipocyte volume correlated positively and Delta cell number correlated negatively with Delta homeostatic model assessment-index and Delta low-density lipoprotein, independent of Delta body fat. Transcripts most significantly correlating with Delta adipocyte 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.