Type 2 diabetes is associated with decreased PGC1α expression in epicardial adipose tissue of patients with coronary artery disease

Inmaculada Moreno-Santos,Juan José Gómez-Doblas,Daniel Castellano,Miguel López-Garrido,Eduardo De Teresa-Galván,María José Mataró,Manuel Jiménez-Navarro,Luis Miguel Pérez-Belmonte,Manuel Macías-González,Pedro L Sánchez-Fernández,Fernando Cardona,Carlos Porras-Martín

doi:10.1186/s12967-016-0999-1

Abstract

BackgroundAlthough recent studies indicate that epicardial adipose tissue expresses brown fat-like genes, such as PGC1α, UCP1 and PRDM16, the association of these genes with type 2 diabetes mellitus (DM2) in coronary artery disease (CAD) remains unknown.MethodsPGC1α, UCP1, and PRDM16 mRNAs expression levels were measured by real-time PCR in epicardial and thoracic subcutaneous adipose tissue from 44 CAD patients (22 with DM2 [CAD-DM2] and 22 without DM2 [CAD-NDM2]) and 23 non-CAD patients (NCAD).ResultsThe CAD-DM2 patients had significantly lower PGC1α and UCP1 expression in epicardial adipose tissue than the CAD-NDM2 and NCAD patients. However, PGC1α and UCP1 mRNA trended upward in subcutaneous adipose tissue from CAD-DM2 patients. At multiple regression analysis, age, body mass index, left ventricular ejection fraction, UCP1 expression of epicardial adipose tissue and diabetes came out to be independent predictors of PGC1α levels. Epicardial adipose tissue PGC1α expression was dependent on the number of injured coronary arteries and logistic regression analysis showed that PGC1α expression in epicardial adipose tissue could exert a protective effect against coronary lesions.ConclusionsDM2 is associated with decreased expression of PGC1α and UCP1 mRNA in epicardial adipose tissue of patients with CAD, likely reflecting a loss of brown-like fat features. Decreased expression of PGC1α in human epicardial adipose tissue is associated with higher prevalence of coronary lesions.

Highlights

Recent studies indicate that epicardial adipose tissue expresses brown fat-like genes, such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), uncoupling protein 1 (UCP1) and PR-domain-missing 16 (PRDM16), the association of these genes with type 2 diabetes mellitus (DM2) in coronary artery disease (CAD) remains unknown
Values are gives as fold increase relative to the non-CAD patients (NCAD) group and differences between groups were considered significant at P < 0.05 (Fig. 1)
We found that epicardial adipose tissue (EAT) PGC1α mRNA levels correlated positively with high-density lipoprotein (HDL)-cholesterol, left ventricular ejection fraction (LVEF), and EAT UCP1 mRNA levels and negatively with body mass index (BMI), circulating triglycerides

Summary

Introduction

Recent studies indicate that epicardial adipose tissue expresses brown fat-like genes, such as PGC1α, UCP1 and PRDM16, the association of these genes with type 2 diabetes mellitus (DM2) in coronary artery disease (CAD) remains unknown. Due to the close anatomical proximity to the heart and the absence of fascial boundaries, EAT has been implicated in the development of coronary disease artery (CAD). Several studies have shown that EAT is associated with the development and progression of coronary atherosclerosis, mainly through a dysbalance of pro/antiinflammatory adipokines production in pathological conditions [2,3,4]. In patients with type 2 diabetes mellitus (DM2), the EAT dysfunction might be the main connection between the diabetic state and complexity of coronary lesions in patients with CAD. DM2 is associated with more extensive CAD, a more aggressive course and greater morbidity and mortality than in coronary patients without DM2 [10]

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