%0 Journal Article %T Inflammatory Macrophage Interleukin-1β Mediates High-Fat Diet-Induced Heart Failure With Preserved Ejection Fraction. %A Liu H %A Huang Y %A Zhao Y %A Kang GJ %A Feng F %A Wang X %A Liu M %A Shi G %A Revelo X %A Bernlohr D %A Dudley SC %J JACC Basic Transl Sci %V 8 %N 2 %D Feb 2023 %M 36908663 %F 9.531 %R 10.1016/j.jacbts.2022.08.003 %X Diabetes mellitus (DM) is a main risk factor for diastolic dysfunction (DD) and heart failure with preserved ejection fraction. High-fat diet (HFD) mice presented with diabetes mellitus, DD, higher cardiac interleukin (IL)-1β levels, and proinflammatory cardiac macrophage accumulation. DD was significantly ameliorated by suppressing IL-1β signaling or depleting macrophages. Mice with macrophages unable to adopt a proinflammatory phenotype were low in cardiac IL-1β levels and were resistant to HFD-induced DD. IL-1β enhanced mitochondrial reactive oxygen species (mitoROS) in cardiomyocytes, and scavenging mitoROS improved HFD-induced DD. In conclusion, macrophage-mediated inflammation contributed to HFD-associated DD through IL-1β and mitoROS production.