Effect of metformin on transcriptome and adipokinome of adipocytes of local fat deposts of patients with ischemic heart disease

Abstract

BACKGROUND: The information available to date on the effect of metformin on the transcriptome and secretory capacity of adipocytes in human adipose tissue (AT) is scarce and contradictory. The study analyzed whether metformin in vitro modulates gene expression and secretion of adiponectin and leptin in the AT of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) localization of patients with ischemic artery disease (IHD).AIM: To assess the effect of metformin at various concentrations (1 and 10 mmol / L) on the level of expression of adiponectin and leptin genes and their content in adipocytes of subcutaneous, epicardial and perivascular AT of patients with IHD.MATERIALS AND METHODS: The study included 134 patients with IHD and indications for direct myocardial revascularization by coronary artery bypass grafting (CABG). During the operation, biopsies of SAT, EAT and PVAT were obtained for 3–5 gram, which served as a source of adipocytes. Isolated adipocytes were cultured for 24 hours with and without metformin (1 and 10 mmol / L). After a day of incubation, the expression of the ADIPOQ and LEP genes and the level of secretion of adiponectin and leptin in the culture medium of adipocytes were determined. Statistical processing was performed using the GraphPad Prism 6 software package (GraphPad Software, La Jolla, CA, USA) and Statistica software, 6.1 (Dell Software, Inc., Round Rock, TX, USA).RESULTS: The adipocytes of the EAT and PVAT of patients with IHD were characterized by an imbalance in the adipokine system, manifested by a low level of ADIPOQ expression and a high LEP expression in comparison with adipocytes of the SAT. Metformin increased the level of ADIPOQ expression and its secretion by adipocytes regardless of their location, while a low concentration (1 mmol / L) in adipocytes of EAT had a stronger effect compared to 10 mmol / L. Metformin had a multidirectional effect on the level of leptin in adipocytes, which depended on their localization: both in low (1 mmol / L) and high concentrations (10 mmol / L), the drug reduced the level of LEP expression and protein secretion in the culture medium of adipocytes of the SAT. EAT had no significant effect on adipocytes. In PVAT, metformin increased the expression and secretion of leptin regardless of concentration.CONCLUSION: Metformin has a direct effect on adipocytes in SAT, EAT, and PVAT and is able to modulate their activity, which is a promising strategy for maintaining the balance of adipokines in AT, especially epicardial and perivascular localization.