Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France.
University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
Int J Obes (Lond). 2019 Jul;43(7):1485-1490. doi: 10.1038/s41366-018-0260-5. Epub 2018 Nov 27.
MicroRNAs have been involved in insulin resistance (IR). As the mechanism whereby niacin, an anti-dyslipidemic agent, leads to IR remains elusive, we sought to identify differentially expressed microRNAs in adipose tissue (AT) of individuals receiving niacin and to explore the link between microRNAs, niacin and IR in human adipocytes.In a double-blind controlled study, 22 obese men received extended-release niacin or placebo over 8 weeks. Bioclinical data and subcutaneous AT biopsies were obtained before and after treatment. AT microRNA expression profiles were determined using RTqPCR for 758 human-specific microRNAs. hMADS adipocytes were treated with niacin, or acipimox (a niacin-like drug without effect on IR), or transfected with miR-502-3p. Glucose uptake and Western blotting were performed.In obese men, insulin sensitivity decreased after niacin treatment. In AT, the expression of 6 microRNAs including miR-502-3p was up-regulated. Treatment of hMADS adipocytes with niacin specifically increased miR-502-3p expression. Acipimox had no effect. Overexpression of miR-502-3p in adipocytes led to reduced insulin-induced glucose uptake and lower insulin-stimulated AKT phosphorylation.Long term niacin treatment altered microRNA expression levels in human AT. Increased miR-502-3p expression may play a role in the mediation of IR due to niacin in adipocytes.The study is registered in Clinical Trials NCT01083329 and EudraCT 2009-012124-85.
微 RNA 已参与胰岛素抵抗 (IR)。由于烟酸作为一种抗血脂药物导致 IR 的机制仍不清楚，我们试图鉴定接受烟酸治疗的个体脂肪组织 (AT) 中差异表达的 microRNAs，并探索 microRNAs、烟酸和人类脂肪细胞中 IR 之间的联系。在一项双盲对照研究中，22 名肥胖男性在 8 周内接受缓释烟酸或安慰剂治疗。治疗前后获得生物临床数据和皮下 AT 活检。使用 RTqPCR 测定 758 个人特异性 microRNAs 的 AT microRNA 表达谱。用烟酸、阿昔莫司（一种对 IR 无影响的烟酸样药物）或 miR-502-3p 转染处理 hMADS 脂肪细胞。进行葡萄糖摄取和 Western 印迹。在肥胖男性中，烟酸治疗后胰岛素敏感性降低。在 AT 中，包括 miR-502-3p 在内的 6 种 microRNAs 的表达上调。烟酸处理 hMADS 脂肪细胞特异性增加 miR-502-3p 的表达。阿昔莫司没有作用。脂肪细胞中 miR-502-3p 的过表达导致胰岛素诱导的葡萄糖摄取减少和胰岛素刺激的 AKT 磷酸化降低。长期烟酸治疗改变了人类 AT 中 microRNA 的表达水平。增加的 miR-502-3p 表达可能在脂肪细胞中由于烟酸介导的 IR 中发挥作用。该研究在 ClinicalTrials.gov 注册为 NCT01083329 和 EudraCT 2009-012124-85。
