Deficiency of liver-X-receptor-α reduces glucose uptake and worsens post-myocardial infarction remodeling

Liver X receptor α (LXRα) is an endogenous protective receptor against ischemic heart diseases. However, whether LXRα regulated glucose metabolism in ischemic heart diseases has not been investigated. In this study we investigated the involvement of LXRα on glucose metabolism in cardiac remodeling after myocardial infarction (MI). MI was induced in mice by permanent ligation of the left anterior descending coronary artery (LCA). Genetic LXRα deletion significantly worsened cardiac remodeling and impaired cardiac function at 4 weeks after MI. Cardiac 18F-fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) demonstrated that the FDG standardized uptake value (SUV) was significantly lower in LXRα^−/− mice as compared to WT mice. Mechanistically, GLUT1/4 and AMPK phosphorylation were significantly downregulated while CD36 expression was markedly upregulated in LXRα^−/− mice. This study demonstrated that deficiency of LXRα decreased glucose uptake after MI, resulting in a metabolic shift that suppressed glucose metabolism, which was in association with adverse cardiac remodeling. - Highlights: • Deficiency of LXRα reduced glucose uptake after myocardial infarction (MI). • Loss of LXRα downregulated GLUT1/4 expressions in response to MI. • Targeting LXRα to promote glucose uptake may protect against cardiac remodeling.