The production and regulation of IGF and IGFBPs in human adipose tissue cultures.
BACKGROUND
Adipocytes express and secrete IGFs and IGFBPs; proteins with important effects on adipocyte homeostasis. However, the factors that control adipocyte generation of IGFs and IGFBPs are not clarified.


OBJECTIVE
To identify regulators of the synthesis of IGFs and IGFBs in adipose tissue.


METHODS
Subcutaneous adipose tissue fragments (500 mg) from 7 healthy lean women were incubated for 48 h following addition of GH (50 μg/l), dexamethasone (DXM, 20 nM), insulin (100 nM), interleukin (IL)-1β (50 ng/l), IL-6 (50 ng/l) and tumor-necrosis factor (TNF)-α (10 ng/l). Outcome parameters included tissue mRNA and culture media IGF and IGFBP levels.


RESULTS
Adipose tissue cultures secreted more IGF-II than IGF-I protein (1.14±0.41 vs. 0.26±0.09 μg/l [mean±SEM]; P<0.02). IGF-I mRNA and protein levels were stimulated by GH (to 340% [153; 477] (median [interquartiles]) and 270±26%, respectively; P<0.003), and inhibited by IL-1β (to 28% [21; 77] and 68±11%, respectively; P<0.003). TNF-α reduced IGF-I and IGF-II protein levels to 51±8% and 69±8%, respectively (P≤0.002), without affecting mRNA levels. IGF protein levels were unaffected by DXM, insulin and IL-6. All IGFBPs IGFBP-1 were expressed. IGFBP-4 was by far the most predominant IGFBP by immunoassay and WLB revealed two bands at 28 and 24 kDa, most likely representing glycosylated and non-glycosylated IGFBP-4.


CONCLUSIONS
Adipose tissue cultures secrete more IGF-II than IGF-I, and predominantly IGFBP-4. The secretion of IGF-I is affected by GH, IL-1β and TNF-α, whereas IGF-II is affected by TNF-α only. Hence, cytokines may control adipocyte homeostasis by affecting local IGF-generation.
The Medical Research Laboratories, Institute of Clinical Medicine & Department of Endocrinology and Internal Medicine, Nørrebrogade, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Mette Faurholdt
MF
Gude
Jan
J
Frystyk
Allan
A
Flyvbjerg
Jens Meldgaard
JM
Bruun
Bjørn
B
Richelsen
Steen Bønløkke
SB
Pedersen
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
C035170:IGF2 protein, human; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D053583:Interleukin-1beta; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II