The production and regulation of IGF and IGFBPs in human adipose tissue cultures

BackgroundAdipocytes 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.AimTo identify regulators of the synthesis of IGFs and IGFBs in adipose tissue.MethodsSubcutaneous 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.ResultsAdipose 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.ConclusionAdipose 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.