Figure 6.

Putative involvement of metformin in cardiac arachidonic metabolism, CYP-derived arachidonic acid metabolites and some cytochrome P450 proteins. The alterations in AA metabolism is manifested in the form of elevated production of anti-inflammatory 14,15-EET, produced by Cyp2c and inhibited formation of pro-inflammatory 20-HETE, produced by Cyp2e. In addition, reduced SCD-1 expression with an inhibited D9D activity index in the myocardium contributes to reduced myocardial accumulation of neutral lipids and toxic lipid intermediates, respectively. Affecting the desaturation system is associated with an altered fatty acid profile in membrane phospholipids in the myocardium, which contributes to an increased proportion of n3-PUFA, resulting in increased membrane fluidity. All these changes, together with markedly elevated Nrf2 expression, contribute to the reduction of cardiac lipotoxicity and inflammation.