FIGURE 4. Glucose regulates direct LXR target genes in vivo.

a, HepG2 cells cultured in 0 mM (white bars), 2 mM (grey bars) or 25 mM (black bars) glucose medium were treated overnight with GW3965 (1 M), 22-(R)-hydroxycholesterol (5 M), or d-glucose (20 mM) and gene expression was analysed using qRT–PCR. Glucose stimulates expression of direct LXR cholesterol homeostasis target genes. Note that efficacy of known LXR ligands increases with increasing glucose concentration. b, Glucose induces LXR target genes in mouse liver. Mice fasted overnight were challenged orally with GW3965 (50 mg kg^-1), or re-fed with a glucose or sucrose diet and killed 6 h later. d-Glucose and GW3965 regulate the same direct LXR targets (genes involved in cholesterol and fatty acid metabolism) as well as indirect carbohydrate metabolism targets. All error bars represent s.d., n = 5–6 mice per group. Asterisk, P < 0.05; double asterisk, P < 0.001 treatment versus fasted.