Cholesin Receptor Signalling is Active in Cardiovascular System-Associated Adipose Tissue and Correlates with SGLT2i Treatment in Patients with Diabetes

Objective: To identify the cholesin receptor-associated genes and clinical factors linked with their expression in cardiovascular system and associated adipose tissues. Research Design and Methods: Right cardiac auricle, aortic wall, saphenous vein and adipose tissue (periaortic-PAT, epicardial-EAT, thymic-TAT) samples were collected during coronary-artery bypass grafting. Results: We included 46 participants [37 male, 23 with type 2 diabetes, median age 68.50 (Q1-Q3: 63.00-72.00) years, BMI 28.39 (26.06-31.49) kg/m2]. GPR146 expression in adipose tissues significantly correlated with BMI, c-peptide, total cholesterol and LDL concentrations. Selected metabolic pathways were significantly and positively enriched in GPR146-dependent manner. GPR146-coexpressed genes contained key regulators of lipid metabolism, and correlated positively with LDL, HDL and total cholesterol concentrations. SGLT2i treatment mirrored GPR146-associated signature in EAT, suggesting potential impact of SGLTi on cholesin-GPR146 network. Conclusions: GPR146 expression is associated with serum lipids and metabolically-relevant transcriptomic changes in adipose tissue, in EAT similar to iSGLT2-associated ones. Funding: The scientific work was funded by the National Science Center Grant Number 2022/45/N/NZ4/01206 awarded to AR, and a grant of Diabetes Poland awarded to AR and co-financed from the state budget funds as part of the Minister of Education and Science program named “Perły Nauki” Project Number PN/01/0025/2022.