LGR6 couples maresin 1 signaling to glycolytic flux and protein lactylation for the rescue of diabetic cardiomyopathy

Background

Diabetic cardiomyopathy (DbCM) is driven by metabolic inflexibility and impaired mitochondrial clearance. While the pro-resolving lipid mediator Maresin 1 (MaR1) shows therapeutic promise, its capacity to correct the underlying metabolic-epigenetic disturbances in DbCM remains undefined. Materials: Db/db mice and palmitic acid (PA)-exposed H9c2 cardiomyocytes were treated with MaR1. Cardiac function and structure were assessed by echocardiography and histological analysis. Myocardial oxidative stress, inflammation, and key molecular pathways were evaluated via immunoblotting, qPCR, immunohistochemistry, and transmission electron microscopy. The role of the putative receptor LGR6 was investigated using siRNA-mediated knockdown.