Irisin mitigates diabetic cardiomyopathy in rats: targeting HMGB1/TLR4/NF-kB signaling pathway

Abstract

Background: Cardiac inflammation, oxidative stress, and myocardial metabolic disruption are among the pathologic abnormalities that can result from diabetic cardiomyopathy (DCM), an independent diabetic cardiac disease. A new myokine called irisin has preventive properties against heart conditions. Objective: to demonstrate the potential underlying processes and cardiovascular protective impact of Irisin in diabetic cardiomyopathy. Material and methods: DCM, DCM+Irisin, and control (10/group) were the three groups into which thirty male albino rats were divided. After eight weeks, assessments of the following were made: LVW/ tibial length, serum glucose, serum insulin, HOMA-IR index, serum glycosylated Hb A1c, serum cholesterol, serum triglyceride, serum cTnI, serum LDH, serum CK-MB, cardiac MDA, cardiac SOD, cardiac TNF-α, cardiac IL-6, cardiac IL-10, cardiac HMGB1 gene expression, cardiac TLR4 gene expression and cardiac NF-kB gene expression. Furthermore, histological and immunohistochemical examinations of the heart and aorta were carried out. Results: The measured LVW/ tibial length, serum glucose, serum Insulin, HOMA-IR index, serum glycosylated Hb A1c, serum cholesterol, serum triglyceride, serum cTnI, serum LDH, serum CK-MB, cardiac MDA, cardiac TNF-α, cardiac IL-6, cardiac gene expression of HMGB1, TLR4 and NF-kB, were all markedly raised in DCM group compared to control, while the DCM group's cardiac SOD, and cardiac IL-10 were substantially lower than those of the control. Additionally there was dramatically downregulated cardiac and aortic NF-kB immunoreaction of DCM group compared to control. Irisin significantly mitigated diabetic cardiomyopathy induced changes.Conclusion: Irisin protects against DCM by downregulating the cardiac HMGB1/TLR4/NF-kB signaling pathway and displaying lipid-lowering, anti-inflammatory and antioxidant impacts.