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?. (1st October 2019)

• Record Type: Journal Article
• Authors: Dozio, Elena; Vianello, Elena; Malavazos, Alexis E.; Tacchini, Lorenza; Schmitz, Gerd; Iacobellis, Gianluca; Corsi Romanelli, Massimiliano M.
• Is Part Of: International journal of cardiology. Volume 292(2019)
• Page Start: 218
• Page End: 224
• Publication Date: 2019-10-01
• Subjects: Epicardial adipose tissue -- Epicardial fat -- GLP-1 receptor -- GLP-2 receptor -- Fatty acid oxidation -- White-to-brown fat differentiation; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2019.04.039
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: 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 analyzed whether 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-1R was directly correlated with genes promoting beta-oxidation and white-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. Highlights: GLP-1 analogs induce a reduction of EAT thickness, independently of weight loss and glucose control. EAT expresses GLP-1R. EAT GLP-1R is associated with genes involved in fatty acid oxidation and white-to-brown fat differentiation. The potential protective effects of GLP-1 analogs on the heart may be mediated by their ability to target EAT GLP-1R.