Irisin: An influential perspective on the protective effect of metformin on aortic and cardiac aging in rats

Aim: Irisin, a polypeptide hormone, demonstrates a protective function in metabolic diseases and has been observed to enhance endothelial functions. It regulates energy metabolism, fat tissue and glucose metabolism. The predictive value of irisin for the effects of metformin on cardiac and aortic aging in an aged rat model was evaluated by quantitative and histological confirmation. Material and Methods: A total of twenty-four rats were used in our study. The subjects were equally distributed among four intervention groups: young control group (<12 months), young-metformin group (<12 months), old-control group (>24 months), and old-metformin group (>24 months). The effect of senescence on the heart and aortic tissues, inflammatory and oxidative stress markers, and proliferation indicators (Ki-67, PDGFR-β, TNF-α, IL-1β, NF-κB, TGF-β, e-NOS, and SOD-1) were evaluated with RT-PCR analyses quantitatively. Serum sampling was conducted to determine irisin levels. A histomorphological and immunhistochemical analysis of the heart and aorta sections was performed. Results: Metformin treatment altered irisin levels in young and old rats compared to controls. Irisin concentrations were higher in metformin-treated rats: 2.57 (0.39) versus 1.89 (0.16) in young rats, and 1.79 (0.31) versus 1.19 (0.22) in old rats (P<0.001 for both). Differences were noted between young-metformin and old-control groups (P=0.002), and old-control and old-metformin groups (P=0.008). Aortic tissue showed significant variations among groups in NF-κB (P=0.024), TGF-β (P<0.001), e-NOS (P=0.001), and SOD-1 (P<0.001) levels. In cardiac tissue, significant differences were observed for Ki-67 (P<0.001), TGF-β (P=0.001), e-NOS (P=0.003), and PDGFR-β (P=0.003) levels. Conclusion: Irisin level was significantly affected by metformin treatment, especially in young rats. Irisin was positively correlated with platelet-derived growth factor receptor-β and oxidative-proinflammatory markers were down-regulated with metformin treatment. Irisin can be viewed as a guide and confirmatory in anti-aging studies, aortic pathologies, and the elucidation of new drug studies and new pathways to confirm cardiac damage.