Fig. 5.
Selective leptin sensitivity arising from maternal diet-induced obesity is mediated via Mc4r PVH. Mice (6 mo) were injected with saline (S, vehicle) or leptin (L, 10 mg/kg, i.p.) after an overnight fast in OffOb- and OffCon-WT, -Mc4rKO, and -Mc4rPVH mice, and FI and BP (MAP) were monitored. (A–C) MAP after leptin challenge in OffOb- vs. OffCon-WT, -Mc4rKO, and -Mc4rPVH mice. MAP returned to baseline (1) in all mice except OffOb-Mc4rPVH. Mc4rKO mice showed no pressor response to leptin. FI (D) and weight gain (E) after an overnight fast in OffOb-WT Mc4rKO and Mc4rPVH offspring are compared with respective controls. Mc4rKO mice were insensitive to the effect of leptin and failed to reduce FI and BW. Data are expressed as mean ± SEM (n = 6–8 per group, sexes combined). *P < 0.001 and #P < 0.05 vs. OffCon using the Student t test. Means not sharing the same letter are significantly different from each other (P < 0.05) by generalized least squares (GLS) regression analysis.