Schematic representation of LXRα-mediated glucose protectionLXRα transcriptionally regulates glycolytic metabolism by targeting glucose utilization at distinct levels. Increased Glut1 and Glut4 enhance glucose uptake, and Pdk4 regulates pyruvate oxidation in mitochondria. Subsequent increases in glycolytic flux activate the HBP, resulting in downstream O-GlcNAc modification of transcription factors inducing natriuretic peptide expression, a putative end effector mediating anti-hypertrophic effects in the heart. ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide; F-6-P, fructose-6-phosphate; Glut, glucose transporter; HBP, hexosamine biosynthesis pathway; Mef2c, myocyte enhancer factor 2C; O-GlcNAc, β-O-linkage of N-acetylglucosamine; PDC, pyruvate dehydrogenase complex; Pdk4, pyruvate dehydrogenase kinase 4. 