title: Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue from obese adolescents: association with insulin resistance and hepatic steatosis.
abstract: OBJECTIVE
  We explored whether the distribution of adipose cell size, the estimated total number of adipose cells, and the expression of adipogenic genes in subcutaneous adipose tissue are linked to the phenotype of high visceral and low subcutaneous fat depots in obese adolescents.
  
  
  METHODS
  A total of 38 adolescents with similar degrees of obesity agreed to have a subcutaneous periumbilical adipose tissue biopsy, in addition to metabolic (oral glucose tolerance test and hyperinsulinemic euglycemic clamp) and imaging studies (MRI, DEXA, (1)H-NMR). Subcutaneous periumbilical adipose cell-size distribution and the estimated total number of subcutaneous adipose cells were obtained from tissue biopsy samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. The adipogenic capacity was measured by Affymetrix GeneChip and quantitative RT-PCR.
  
  
  RESULTS
  Subjects were divided into two groups: high versus low ratio of visceral to visceral + subcutaneous fat (VAT/[VAT+SAT]). The cell-size distribution curves were significantly different between the high and low VAT/(VAT+SAT) groups, even after adjusting for age, sex, and ethnicity (MANOVA P = 0.035). Surprisingly, the fraction of large adipocytes was significantly lower (P < 0.01) in the group with high VAT/(VAT+SAT), along with the estimated total number of large adipose cells (P < 0.05), while the mean diameter was increased (P < 0.01). From the microarray analyses emerged a lower expression of lipogenesis/adipogenesis markers (sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase) in the group with high VAT/(VAT+SAT), which was confirmed by RT-PCR.
  
  
  CONCLUSIONS
  A reduced lipo-/adipogenic capacity, fraction, and estimated number of large subcutaneous adipocytes may contribute to the abnormal distribution of abdominal fat and hepatic steatosis, as well as to insulin resistance in obese adolescents.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Romy
authors.initials: R
authors.lastname: Kursawe
authors.forename: Markus
authors.initials: M
authors.lastname: Eszlinger
authors.forename: Deepak
authors.initials: D
authors.lastname: Narayan
authors.forename: Teresa
authors.initials: T
authors.lastname: Liu
authors.forename: Merlijn
authors.initials: M
authors.lastname: Bazuine
authors.forename: Anna M G
authors.initials: AM
authors.lastname: Cali
authors.forename: Ebe
authors.initials: E
authors.lastname: D'Adamo
authors.forename: Melissa
authors.initials: M
authors.lastname: Shaw
authors.forename: Bridget
authors.initials: B
authors.lastname: Pierpont
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Cushman
authors.forename: Arthur
authors.initials: A
authors.lastname: Sherman
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
mesh_terms: D050153:Abdominal Fat / Q000473:pathology / Q000503:physiopathology; D000293:Adolescent; D001706:Biopsy; D049628:Body Size; D003971:Diastole; D005234:Fatty Liver / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000033:anatomy & histology* / Q000473:pathology*; D008055:Lipids / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009765:Obesity / Q000473:pathology*; D044469:Racial Groups; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D050507:Subcutaneous Fat, Abdominal / Q000033:anatomy & histology* / Q000473:pathology*; D013599:Systole; D049629:Waist-Hip Ratio
chemical_list: D007328:Insulin; D008055:Lipids
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