Figure 1.

Metabolism and Immunity Coupling in HFpEF. Metainflammation is a chronic low-grade systemic state of inflammation associated with obesity. Systemic inflammation has been recognized as a cause of HFpEF through: (i) microvascular dysfunction and downregulation of NO/cGMP signalling; (ii) nitrosative stress and protein quality control impairment, altering the dynamic state of cardiomyocyte molecular constituents. In addition, nutrient overload in obesity has immune and metabolic consequences on insulin sensitivity. Insulin resistance limits cardiac metabolic flexibility and hampers energy provision (iii).