Epicardial adipose tissue GLP-1 receptor is associated with genes involved in fatty acid oxidation and white-to-brown fat differentiation: A target to modulate cardiovascular risk?
Epicardial adipose tissue GLP-1 receptor is associated with genes involved in fatty acid oxidation and white-to-brown fat differentiation: A target to modulate cardiovascular risk?
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DOI：
10.1016/j.ijcard.2019.04.039
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发表时间：
2019-10-01
影响因子：
3.5
通讯作者：
Romanelli, Massimiliano M. Corsi
中科院分区：
文献类型：
--
作者：
Dozio, Elena;Vianello, Elena;Romanelli, Massimiliano M. Corsi
背景：心外膜脂肪组织（EAT）是心血管疾病的危险因素。胰高血糖素样肽1类似物（GLP-1A）可能具有有益的心血管作用并减少EAT，可能贯穿靶向GLP-1受体（GLP-1 R）。然而，EAT GLP-1 R、GLP-2 R的作用及其与脂肪形成和脂肪酸（FA）代谢相关的EAT基因的相互作用尚不清楚。方法：收集17例冠状动脉疾病（coronary artery disease，CAD）患者的EAT标本，采用基因芯片技术检测GLP-1 R、GLP-2 R及脂肪代谢相关基因的表达。超声心动图测量EAT厚度。结果：EAT GLP-1 R与促进β-氧化和白褐色脂肪细胞分化的基因正相关，与促脂肪形成基因负相关。GLP-2 R与参与脂肪形成和脂质合成的基因呈正相关，与促进β-氧化的基因呈负相关。GLP-1和GLP-2水平高于CAD CTR和患者更大的EAT thickness.Conclusions：GLP-1类似物可能靶向EAT GLP-1 R，从而减少局部脂肪生成，提高脂肪利用率和诱导棕色脂肪分化。由于EAT与心肌和冠状动脉直接相邻，GLP-1激活的有益作用可能延伸至心脏。循环GLP-1和GLP-2以及EAT GLP-2 R水平升高可能是与CAD和EAT扩张相关的代偿机制，但这些观察结果的意义需要进一步研究。(C)2019 Elsevier B. V.版权所有。
Background: Epicardial adipose tissue (EAT) is a risk factor for cardiovascular diseases. Glucagon-like peptide 1 analogs (GLP-1A) may have beneficial cardiovascular effects and reduce EAT, possibly throughout targeting GLP-1 receptor (GLP-1R). Nevertheless, the role of EAT GLP-1R, GLP-2R and their interplay with EAT genes involved in adipogenesis and fatty acid (FA) metabolism are unknown. We analyzedwhether EAT transcriptome is related to GLP-1R/GLP-2R gene expression, and GLP-1/GLP-2 plasma levels in coronary artery disease patients (CAD).Methods: EAT was collected from 17 CAD patients undergoing CABG for microarray analysis of GLP-1R, GLP-2R and genes involved in FA metabolism and adipogenesis. EAT thickness was measured by echocardiography. GLP-1 and GLP-2 levels were quantified by ELISA in CAD and healthy subjects (CTR).Results: EAT GLP-1Rwas directly correlated with genes promoting beta-oxidation andwhite-to-brown adipocyte differentiation, and inversely with pro-adipogenic genes. GLP-2R was positively correlated with genes involved in adipogenesis and lipid synthesis, and inversely with genes promoting beta-oxidation. GLP-1 and GLP-2 levels were higher in CAD than CTR and in patients with greater EAT thickness.Conclusions: GLP-1 analogs may target EAT GLP-1R and therefore reduce local adipogenesis, improve fat utilization and induce brown fat differentiation. As EAT lies in direct contiguity to myocardium and coronary arteries, the beneficial effects of GLP-1 activation may extent to the heart. The increased levels of circulating GLP-1 and GLP-2 and EAT GLP-2R may be compensatory mechanisms related to CAD and also EAT expansion, but the meaning of these observations needs to be further investigated. (C) 2019 Elsevier B.V. All rights reserved.