Vangaveti Venkat, Shashidhar Venkatesh, Collier Fiona, Hodge Jason, Rush Catherine, Malabu Usman, Baune Bernhard, Kennedy Richard Lee
Room 114, Building 47, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia 4814, Australia.
College of Medicine and Dentistry, James Cook University, Queensland, Australia.
Ther Adv Endocrinol Metab. 2018 May;9(5):137-150. doi: 10.1177/2042018818759894. Epub 2018 Feb 27.
Both activation of monocytes and increased serum fatty acid binding protein-4 (FABP4) occur in diabetes and are associated with increased atherosclerosis. The oxidized lipid, 9-hydroxyoctadecadienoic acid (9-HODE) increases FABP4 in macrophages, and is a ligand for G protein-coupled receptor 132 (GPR132). We investigated the involvement of GPR132 in mediating the 9-, 13-HODE stimulation of FABP4 secretion, and whether GPR132 expression is increased in monocytes from patients with type 2 diabetes.
The effects of siRNA silencing of GPR132 gene and of the PPAR-γ antagonist T0070907 were studied in THP-1 cells. Serum levels of FABP4 and other adipokines were measured in patients with diabetes, and monocyte subpopulations were analyzed using flow cytometry. GPR132 mRNA was quantified in isolated CD14 cells.
9-HODE and 13-HODE increased FABP4 expression in THP-1 monocytes and macrophages, and also increased GPR132 expression. Silencing of GPR132 did not influence the increase in FABP4 with 9-HODE, 13-HODE, or rosiglitazone (ROSI). By contrast, T0070907 inhibited the effect of all three ligands on FABP4 expression. Diabetic subjects had increased serum FABP4, and activated monocytes. They also expressed higher levels of GPR132 mRNA in CD14 cells.
We conclude that GPR132 is an independent monocyte activation marker in diabetes, but does not contribute to PPAR-γ-mediated induction of FABP4 by HODEs.
单核细胞活化和血清脂肪酸结合蛋白4（FABP4）升高均出现在糖尿病患者中，且与动脉粥样硬化增加相关。氧化脂质9-羟基十八碳二烯酸（9-HODE）可增加巨噬细胞中的FABP4，并且是G蛋白偶联受体132（GPR132）的配体。我们研究了GPR132在介导9-、13-HODE刺激FABP4分泌中的作用，以及2型糖尿病患者单核细胞中GPR132表达是否增加。
在THP-1细胞中研究了GPR132基因的siRNA沉默和PPAR-γ拮抗剂T0070907的作用。测定了糖尿病患者血清中FABP4和其他脂肪因子的水平，并使用流式细胞术分析了单核细胞亚群。对分离出的CD14细胞中的GPR132 mRNA进行定量。
9-HODE和13-HODE增加了THP-1单核细胞和巨噬细胞中FABP4的表达，也增加了GPR132的表达。GPR132沉默不影响9-HODE、13-HODE或罗格列酮（ROSI）引起的FABP4增加。相比之下，T0070907抑制了所有三种配体对FABP4表达的影响。糖尿病患者血清FABP4升高，单核细胞活化。他们的CD14细胞中GPR132 mRNA表达水平也更高。
我们得出结论，GPR132是糖尿病中一个独立的单核细胞活化标志物，但不参与HODEs通过PPAR-γ介导的FABP4诱导过程。
