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?

Int J Cardiol. 2019 Oct 1:292:218-224. doi: 10.1016/j.ijcard.2019.04.039. Epub 2019 Apr 15.

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.

Keywords: Epicardial adipose tissue; Epicardial fat; Fatty acid oxidation; GLP-1 receptor; GLP-2 receptor; White-to-brown fat differentiation.

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism*
  • Acetyl-CoA C-Acyltransferase / genetics
  • Acetyl-CoA C-Acyltransferase / metabolism*
  • Adipose Tissue, Brown / diagnostic imaging
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / diagnostic imaging
  • Adipose Tissue, White / metabolism*
  • Adult
  • Aged
  • Anthropometry / methods
  • Carbon-Carbon Double Bond Isomerases / genetics
  • Carbon-Carbon Double Bond Isomerases / metabolism*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnostic imaging
  • Cardiovascular Diseases / genetics
  • Enoyl-CoA Hydratase / genetics
  • Enoyl-CoA Hydratase / metabolism*
  • Female
  • Glucagon-Like Peptide-1 Receptor / blood*
  • Glucagon-Like Peptide-1 Receptor / genetics
  • Humans
  • Male
  • Middle Aged
  • Pericardium / diagnostic imaging
  • Pericardium / metabolism*
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / metabolism*
  • Risk Factors

Substances

  • Glucagon-Like Peptide-1 Receptor
  • fatty acid oxidation complex
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Acetyl-CoA C-Acyltransferase
  • Enoyl-CoA Hydratase
  • Racemases and Epimerases
  • Carbon-Carbon Double Bond Isomerases