Gude Mette Faurholdt, Frystyk Jan, Flyvbjerg Allan, Bruun Jens Meldgaard, Richelsen Bjørn, Pedersen Steen Bønløkke
The Medical Research Laboratories, Institute of Clinical Medicine & Department of Endocrinology and Internal Medicine, Nørrebrogade, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Growth Horm IGF Res. 2012 Dec;22(6):200-5. doi: 10.1016/j.ghir.2012.09.004. Epub 2012 Oct 16.
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.
To identify regulators of the synthesis of IGFs and IGFBs in adipose tissue.
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.
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.
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.
脂肪细胞表达并分泌胰岛素样生长因子（IGFs）和胰岛素样生长因子结合蛋白（IGFBPs）；这些蛋白对脂肪细胞内稳态具有重要影响。然而，控制脂肪细胞生成IGFs和IGFBPs的因素尚不清楚。
鉴定脂肪组织中IGFs和IGFBPs合成的调节因子。
将7名健康瘦女性的皮下脂肪组织碎片（500mg）加入生长激素（GH，50μg/L）、地塞米松（DXM，20nM）、胰岛素（100nM）、白细胞介素（IL）-1β（50ng/L）、IL-6（50ng/L）和肿瘤坏死因子（TNF）-α（10ng/L）后孵育48小时。观察指标包括组织mRNA以及培养基中IGF和IGFBP水平。
脂肪组织培养物分泌的IGF-II蛋白多于IGF-I蛋白（1.14±0.41对0.26±0.09μg/L[平均值±标准误]；P<0.02）。GH刺激IGF-I mRNA和蛋白水平（分别至340%[153；477]（中位数[四分位数间距]）和270±26%；P<0.003），而IL-1β抑制它们（分别至28%[21；77]和68±11%；P<0.003）。TNF-α将IGF-I和IGF-II蛋白水平分别降至51±8%和69±8%（P≤0.002），但不影响mRNA水平。IGF蛋白水平不受DXM、胰岛素和IL-6的影响。所有IGFBPs（IGFBP-1）均有表达。免疫测定显示IGFBP-4是迄今为止最主要的IGFBP，WLB显示在28kDa和24kDa处有两条带，最可能代表糖基化和非糖基化的IGFBP-4。
脂肪组织培养物分泌的IGF-II多于IGF-I，且主要是IGFBP-4。IGF-I的分泌受GH、IL-1β和TNF-α影响，而IGF-II仅受TNF-α影响。因此，细胞因子可能通过影响局部IGF生成来控制脂肪细胞内稳态。
