Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Diabetes Metab Res Rev. 2019 Jan;35(1):e3074. doi: 10.1002/dmrr.3074. Epub 2018 Oct 4.
Experimental and epidemiological studies reported controversial data on the role of omentin in type 2 diabetes and cardiovascular diseases. This study aimed to characterise the impact of omentin on the secretome of human adipocytes to analyse the enrichment of these proteins in metabolic and cellular signalling pathways underlying its physiological function.
MATERIAL/METHODS: Differentiated primary human adipocytes were treated without or with 500 or 2000 ng/mL omentin for 24 hours. The secretome was analysed by liquid chromatography coupled tandem-mass spectrometry. Differences in protein secretion between untreated and omentin-treated adipocytes were compared using a paired t-test. Other potential upstream regulators and the overrepresentation in canonical pathways of omentin-stimulated proteins were analysed using Ingenuity Pathway Analysis.
The supernatant of adipocytes contained 3493 proteins, of which 140 were differentially secreted by both concentrations of omentin compared with untreated adipocytes. Among the most strongly increased proteins, tumour necrosis factor-inducible gene 6 protein (TNFAIP6) was increased by 140-fold in the supernatant. Omentin-regulated proteins were overrepresented in seven canonical pathways including eukaryotic initiation factor 2 signalling, complement system, and inhibition of matrix metalloproteases. We further identified 25 other potential upstream activators of omentin-regulated proteins, mainly pro-inflammatory cytokines and transcription regulators including NFκB.
In differentiated human adipocytes, the release of the anti-inflammatory TNFAIP6 might be part of a counterregulatory response to the pro-inflammatory action of omentin. Omentin-regulated proteins were overrepresented in pathways indicating cellular stress, a pro-inflammatory environment and a crosstalk with other organs. Other potential activators of omentin-regulated proteins point towards a central role of NFκB activation in the omentin-induced secretory process.
实验和流行病学研究报告了关于网膜素在 2 型糖尿病和心血管疾病中的作用的有争议的数据。本研究旨在描述网膜素对人脂肪细胞分泌组的影响，分析这些蛋白质在其生理功能相关的代谢和细胞信号通路中的富集情况。
材料/方法：分化的原代人脂肪细胞在无或有 500 或 2000ng/ml 网膜素的条件下处理 24 小时。通过液相色谱-串联质谱分析分泌组。使用配对 t 检验比较未处理和网膜素处理的脂肪细胞之间分泌蛋白的差异。使用 IPA 分析其他潜在的上游调节剂和网膜素刺激蛋白在经典途径中的过表达情况。
脂肪细胞的上清液中含有 3493 种蛋白质，其中有 140 种在两种浓度的网膜素处理下与未处理的脂肪细胞相比差异分泌。在增加最多的蛋白质中，肿瘤坏死因子诱导基因 6 蛋白（TNFAIP6）在上清液中的表达增加了 140 倍。网膜素调节蛋白在包括真核起始因子 2 信号通路、补体系统和基质金属蛋白酶抑制在内的 7 个经典通路中过表达。我们进一步鉴定了 25 种其他潜在的网膜素调节蛋白的上游激活剂，主要是促炎细胞因子和转录调节剂，包括 NFκB。
在分化的人脂肪细胞中，抗炎性 TNFAIP6 的释放可能是对网膜素促炎作用的一种代偿性反应的一部分。在表明细胞应激、促炎环境和与其他器官相互作用的通路中，网膜素调节蛋白过表达。其他潜在的网膜素调节蛋白的激活剂表明 NFκB 激活在网膜素诱导的分泌过程中起着核心作用。
