Glucose-dependent insulinotropic polypeptide modifies adipose plasticity and promotes beige adipogenesis of human omental adipose-derived stem cells
Glucose-dependent insulinotropic polypeptide modifies adipose plasticity and promotes beige adipogenesis of human omental adipose-derived stem cells
复制标题
葡萄糖依赖性促胰岛素多肽改变脂肪可塑性并促进人网膜脂肪干细胞的米色脂肪形成
DOI：
10.1096/fj.201903253r
复制
发表时间：
2021-05-01
期刊：
影响因子：
4.8
通讯作者：
Li, Yanbing
中科院分区：
文献类型：
--
作者：
Chen, Xueying;He, Xiaoying;Li, Yanbing
位于白色脂肪组织（WAT）中的脂肪细胞前体（AP）在脂肪可塑性和布朗宁中具有重要的功能。以AP为靶点改变脂肪形成或WAT布朗宁是一种很有前途的抗肥胖药物机制。本文探讨了肠源性肽葡萄糖依赖性促胰岛素多肽（GIP）对从网膜分离的人脂肪间充质干细胞（hADSCs）的体外作用及其机制。将hADSC用IOOnM GIP与或不与等摩尔浓度的GIP 3 -42（GIP受体拮抗剂）共处理，随后在体外进行检查。CCK-8、EdU掺入和流式细胞术测定用于评估细胞增殖。Annexin V FTIC/PI双染、TUNEL染色、Western blot检测细胞凋亡。通过Western blot、实时荧光定量PCR、油红O染色、线粒体染色和线粒体DNA分析来反映脂肪生成。结果表明，GIP通过多效作用促进hADSCs增殖，抑制hADSCs凋亡。此外，GIP通过加速有丝分裂克隆扩增（MCE）、上调核心脂肪形成调节因子（C/EBP α和PPAR γ）、增加米色相关基因（UCP 1、PGC 1 α和PRDM 16）、增加线粒体含量和改善米色脂肪细胞功能，促进从头米色脂肪形成。本研究为GIP在肥胖症治疗中的临床应用提供了理论依据。
The adipocyte precursors (APs) located in white adipose tissue (WAT) are functionally significant in adipose plasticity and browning. Modifying adipogenesis or WAT browning targeted on APs is a promising mechanism for anti-obesity drug. We herein explored the in vitro actions and mechanisms of glucose-dependent insulinotropic polypeptide (GIP), a gut-derived peptide, in human adipose-derived mesenchymal stem cells (hADSCs) isolated from omentum. The hADSCs were cotreated with 100 nM GIP with or without equimolar concentration of GIP3-42 (a GIP receptor antagonist), and subsequently examined in vitro. CCK-8, EdU incorporation, and flow cytometry assays were used to assess cellular proliferation. Annexin V FTIC/PI double stain, TUNEL staining, and Western blot were applied for apoptosis evaluation. Adipogenesis was reflected by Western blot, real-time PCR, Oil Red O staining, mitochondrial staining, and mitochondrial DNA analysis. Results showed that GIP promoted proliferation and inhibited apoptosis of hADSCs via pleiotropic effects. Besides, GIP facilitated de novo beige adipogenesis, by accelerating mitotic clonal expansion (MCE), upregulating core adipogenic regulators (C/EBP alpha and PPAR gamma), augmenting beige-related genes (UCP1, PGC1 alpha, and PRDM16), increasing mitochondrial content and improving beige adipocyte functionalities. Above all, our study expands knowledge on the mechanisms of GIP modifying adipogenesis especially in inducing beige adipogenesis, and thus provides a theoretical support for clinical usage of GIP on obesity treatment.