Figure 4. Glucose metabolites mediate glucose regulation of hypothalamic HIF.

(A&B) 24-h fasted C57BL/6 mice received third-ventricle infusion of glucose versus vehicle. Hypothalami were harvested and measured for tissue contents of fumarate (A) and succinate (B). * p<0.05; n = 5–6 per group. Error bars reflect mean ± SEM. (C&D) 24-h fasted C57BL/6 mice received third-ventricle infusion of diethyl fumarate (Fum) or diethyl succinate (Suc) or control vehicle (Veh). Hypothalami were harvested for Western blot analysis of HIF2α protein (C) and GHO assay for PHD activities (D). Bar graphs: HIF2α protein levels (C) and PHD activities (D) were quantitated and analyzed statistically. ** p<0.01; n = 5–6 per group. Error bars reflect mean ± SEM. (E&F) 24-h fasted POMC/HIFβ^lox/lox mice (P/HIFβ^l/l) and control littermates HIFβ^lox/lox mice (HIFβ^l/l) received third-ventricle injection of diethyl fumarate (Fum) (E), diethyl succinate (Suc) (F), or vehicle (Veh) (E&F), and subsequently monitored for food intake for 6 h. * p<0.05; ** p<0.01; n = 7–10 per group. Error bars reflect mean ± SEM. (A–F) All mice were adult males and normal chow-fed.