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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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.
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A correlation between epicardial fat GLP-1R and genes encoding for brown fat activity and fatty acid oxidation has been reported.
“Interestingly, a correlation between epicardial fat GLP-1R and genes encoding for brown fat activity and fatty acid oxidation has been recently reported [26].”
From Effects of Semaglutide Versus Dulaglutide on Epicardial Fat Thickness in Subjects with Type 2 Diabetes and Obesity (2020) · cites this paper as [26]
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Drug-induced metabolic alterations in adipose tissue - with an emphasis in epicardial adipose tissue
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- Authors
- Dozio, E., Vianello, E., Malavazos, A. E., Tacchini, L., Schmitz, G., Iacobellis, G., & Corsi Romanelli, M. M.
- Affiliations
- University of Milan (IT)
- IRCCS Policlinico San Donato (IT)
- University of Regensburg (DE)
- University of Miami (US)
- Corresponding author
- Dozio, Elena
- ORCID
- Venue
- International Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 292
- Pages
- 218-224
- ISSN
- 0167-5273 (ISSN-L)
- OpenAlex
- W2937422733
- Cited by
- 118
- References
- 41
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 20 · 2023: 15 · 2022: 14 · 2021: 9 · 2020: 11 · 2019: 5
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- International Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- Fondazione E. A. Fiera Internazionale di Milano
- Italian Ministry of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Pharmacology › Apelin-related biomedical research
- Keywords
- epicardial adipose tissue, GLP-1 receptor, GLP-2 receptor, glucagon-like peptide-1, glucagon-like peptide-2, coronary artery disease, fatty acid beta-oxidation, adipogenesis, lipogenesis, EAT thickness, cardiovascular risk, GLP-1 analogues
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Acetyl-CoA C-Acyltransferase, Adult, Aged, Anthropometry, Adipose Tissue, Brown, Cardiovascular Diseases, Enoyl-CoA Hydratase, Female, Humans, Male, Middle Aged, Pericardium, Risk Factors, 3-Hydroxyacyl CoA Dehydrogenases, Carbon-Carbon Double Bond Isomerases, Racemases and Epimerases, Adipose Tissue, White
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