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Endocrine Abstracts (2013) 32 P622 | DOI: 10.1530/endoabs.32.P622

ECE2013 Poster Presentations Growth hormome IGF axis – basic (16 abstracts)

A comparison of the in vitro production of IGFs, IGFBP-4 and PAPP-A in cultures of visceral and subcutaneous adipose tissue fragments from obese subjects

Jan Frystyk 1 , Mette Faurholdt Gude 1 , Rikke Hjortebjerg , Claus Oxvig 2 & Steen Bønløkke Pedersen 3


1Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark; 2Department of Molecular Biology and Genetics, Faculty of Science and Technology, Aarhus University, Aarhus, Denmark; 3Department of Endocrinology and Internal Medicine, Tage Hansens-Gade, Aarhus University Hospital, Aarhus, Denmark.


Background: Visceral adipose tissue (VAT) is less insulin sensitive and more harmful than subcutaneous adipose tissue (SAT). In adipocytes, IGF1 receptor signaling has been linked to insulin resistance, but it is unknown whether VAT and SAT also differ in production of IGFs. Therefore, we compared IGFs, IGFBP-4 and PAPP-A production in cultured fragments of VAT and SAT from obese subjects.

Methods: VAT and SAT was collected perioperatively during elective bariatric surgery from 17 women and 9 men (mean±S.E.M.: age 38.7±1.9 years, BMI 39.8±0.9 kg/m2). Culture media collected after 48 h of incubation (500 mg tissue fragments) without (baseline) and with GH (100 μg/l) were compared for concentrations of IGFs, IGFBP-4, PAPP-A and bioactive IGF1 as measured by IGF1 receptor bioassay.

Results: VAT and SAT produced similar amounts of IGF1 at baseline (mean and inter-quartiles: 0.25 (0–0.56) vs 0.06 (0–0.23) μg/l), but VAT produced more IGF1 than SAT after GH stimulation (0.58 (0.12–1.63) vs 0.30 (0.08–0.59) μg/l, P<0.05). IGF2 production was markedly higher in VAT than SAT (2.66 (1.47–3.84) vs 1.65 (1.09–2.21) μg/l, P<0.05), and in both compartments, baseline IGF2 production exceeded that of IGF1 (P<0.0001). VAT produced fourfold more PAPP-A than SAT (5.16 (4.20–7.00) vs 1.16 (0.96–1.56) μg/l, P<0.05). VAT also produced more IGFBP-4 (45.7 (24.5–69.3) vs 22.7 (18.2–37.7) μg/l, P<0.05). In accordance with these observations, levels of bioactive IGF1 were higher in media from VAT than SAT at baseline (0.13 (0.03–0.19) vs 0.06 (0.05–0.10), P<0.05) as well as after GH stimulation (0.22 (0.10–0.37) vs 0.11 (0.05–0.18) μg/l, P<0.05).

Conclusion: VAT produced markedly more IGF2, PAPP-A and IGFBP-4 than SAT, resulting in a higher media IGF1 bioactivity. Furthermore, VAT was more sensitive to GH than SAT. Our data suggest that PAPP-A may control IGF-action in adipose tissue, in particularly in VAT. This mechanism may have effects on local insulin sensitivity.

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