Ruxolitinib blocks postprandial leptin signaling in the hypothalamus. (A) Schematic localizing the LEPR-expressing neurons within the ventromedial hypothalamus (VMH) and arcuate nucleus (ARC). The lower right subpanel represents the region shown in Panel B. (B) A representative image is shown of an 8-week-old male C57BL6/J fasted mouse treated with Leptin (scale bar, 200 μm). The inset box (dashed) shows the region analyzed in panels C-D. (C) Representative images of ARC from mice that were Fasted, Fasted+Lep, Fed, and Fed+Rux (scale bar, 50 μm). (D) The quantile normalized segmented nuclear pSTAT3 signal intensity is shown for replicate animals treated as described (n = 3-5 mice per group, statistical significance of key differences indicated, t test ***P < 10⁻¹⁵). All experiments were performed in accordance with institutional guidelines and were approved by the International Animal Care and Use Committee and in compliance with the Research Animal Resource Center in the Weill Cornell vivarium. DMH, dorsomedial hypothalamus; NS, not significant.