title: PAPP-A, IGFBP-4 and IGF-II are secreted by human adipose tissue cultures in a depot-specific manner.
abstract: OBJECTIVE
  Adipose tissue secretes pregnancy-associated plasma protein-A (PAPP-A), which may increase local IGF action through cleavage of IGF-binding protein-4 (IGFBP-4). We tested whether this mechanism was operational in human visceral and subcutaneous adipose tissue (i.e. VAT and SAT).
  
  
  METHODS
  Explants of VAT and SAT from 26 obese subjects (hereof 17 women, BMI 39.5 (37.2; 42.8) kg/m2(median (25%; 75% confidence interval) and SAT from eight lean, age-matched women (BMI 23.6 (22.4; 24.9) kg/m2) were incubated with or without GH (100 µg/L) and the media were harvested.
  
  
  METHODS
  Media were assessed for concentrations of PAPP-A, intact and PAPP-A-cleaved IGFBP-4, IGF-I and IGF-II, and IGF-I receptor (IGF-IR) activation by bioassay.
  
  
  RESULTS
  In obese subjects, VAT media contained higher concentrations than SAT of PAPP-A (4.4-fold) and both PAPP-A-generated IGFBP-4 fragments (C-terminal: 3.3-fold, N-terminal: 1.5-fold) (all P < 0.0005). Intact IGFBP-4 levels were similar in SAT and VAT. VAT media contained elevated IGF-II (1.4-fold; P < 0.005), but similar IGF-I concentrations compared with SAT. Still, VAT media contained a 1.8-fold increased ability to stimulate the IGF-IR (P < 0.005). IGF-I protein concentration and IGF-IR activation increased more in VAT media than SAT media following GH stimulation (both P < 0.05). At baseline, SAT media protein levels from lean and obese women were similar, with the exception of PAPP-A being 1.8-fold elevated in VAT media (P < 0.05). GH induced a similar increase in IGF-I media levels in SAT from obese and lean women.
  
  
  CONCLUSIONS
  Human adipose tissue cultures secrete enzymatically active PAPP-A, IGFBP-4 and IGF-II in a depot-specific manner, suggesting differential regulation of IGF activity. Further, IGF-II appears to be more prominent than IGF-I. Finally, VAT appears more GH responsive than SAT.
authors: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus C, Denmark.
authors: Mette Faurholdt
authors: MF
authors: Gude
authors: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus C, Denmark.|Danish Diabetes AcademyOdense, Denmark.
authors: Rikke
authors: R
authors: Hjortebjerg
authors: Department of Molecular Biology and GeneticsFaculty of Science and Technology, Aarhus University, Aarhus C, Denmark.
authors: Claus
authors: C
authors: Oxvig
authors: Departments of Abdominal Surgery.
authors: Anne Anker
authors: AA
authors: Thyø
authors: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus C, Denmark.
authors: Nils Erik
authors: NE
authors: Magnusson
authors: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus C, Denmark.
authors: Mette
authors: M
authors: Bjerre
authors: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus C, Denmark.|Endocrinology and Internal MedicineAarhus University Hospital, Aarhus C, Denmark.
authors: Steen Bønløkke
authors: SB
authors: Pedersen
authors: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus C, Denmark Frystyk@clin.au.dk.|Endocrinology and Internal MedicineAarhus University Hospital, Aarhus C, Denmark.
authors: Jan
authors: J
authors: Frystyk
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D005260:Female; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000601:surgery; D009924:Organ Culture Techniques; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*
chemical_list: C035170:IGF2 protein, human; D018974:Insulin-Like Growth Factor Binding Protein 4; D007335:Insulin-Like Growth Factor II; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human