P3482Leptin, receptor to leptin and expression in adipocytes isolated from different adipose depots in patients with ischemic heart disease

Abstract

Abstract Purpose To study the peculiarities of the content of leptin and the leptin receptor in adipocyte culture of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) adipose tissue and the expression of their genes. Methods 29 patients with coronary heart disease were examined. Adipocytes were isolated from SAT, EAT and PVAT samples obtained during coronary artery bypass grafting, followed by evaluation (after 24 hours) of the leptin concentration (Human resistin ELISA, R&D Systems, USA) and leptin gene expression in cell culture. Magnetic resonance imaging (MRI) was used to determine the area of the visceral (VAT) and subcutaneous adipose tissue (SAT) of the abdominal region, the thickness of epicardial adipose tissue (EAT). The calculation of the free leptin index (FLI) was determined by the formula: leptin/SOB-R * 100. Leptin resistance was defined as an FLI >0.25. All study was carried out in compliance with the Helsinki Declaration, and its protocol was approved by the Ethical Committee of Research Institute. Statistical analysis was performed using Statistica 10.0. Results In adipocytes of EAT, leptin secretion was 1.2 times higher than in adipocytes of PVAT, which is consistent with the expression of the leptin gene. The content of leptin soluble receptor was opposite in the adipocytes of PVAT higher than in EAT and SAT 2.3 and 3.1 times, respectively. At the same time, the index of free leptin was higher in SAT adipocytes 1.3 and 3.2 times in comparison with EAT and PVAT. The correlation analysis confirmed the relationship between EAT thickness and the serum concentrations of leptin. Thus, in patients with VO, the leptin concentration had a negative dependence on the thickness of the left and right ventricle (r=−0.28, p=0.02; r=−0.33, p=0.02, respectively). A negative dependence on the EAT thickness was also established for the FLI (r=−0.28; p=0.03). PVAT of the abdominal aorta is similar to the properties of visceral AT. An analysis of the possible relationship between perivascular adipocytes and adipokine exchange rates showed a direct relationship between the volume PVAT of the abdominal aortic ventricle and leptin (r=0.44, p=0.01), as well as the FLI (r=0.56; p=0.03). Conclusion Adipocytes SAT, EAT and PVAT differed in the level of secretion of leptin. In epicardial and, to a greater extent, in perivascular adipocytes, a protective mechanism against a high concentration of leptin was observed due to increased secretion of the soluble receptor to leptin. The high content of leptin and the low soluble receptor for leptin led to the development of leptin resistance, which was more pronounced in the culture of adipocytes SAT. Meanwhile, the EAT thickness was inversely related to the concentration of leptin and the FLI index (one of the main leptin-resistance markers).