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. 2016 Oct 6;113(43):12298–12303. doi: 10.1073/pnas.1607464113

Fig. 3.

Fig. 3.

Mc4r deletion (Mc4rKO) blunts the MAP in OffOb, whereas reactivation of Mc4r in the PVH completely rescued the increased MAP. Data in each panel were collected as average 24-h recordings from 6-mo-old male and female OffOb (black)- and OffCon (white)-WT, -Mc4rKO, and -Mc4rPVH mice. MAP (A and D), HR (B and E), and LF/HF ratio (C and F; LF, 0.04–0.15; HF, 0.15–0.40). *P < 0.001, †P < 0.01, and #P < 0.05 vs. OffCon; $P < 0.05 vs. OffOb-WT using the Student t test (n = 6–8 per group, mean ± SEM). (G–I) MAP responses to MTII challenge (Mc3/4r agonist, 10 mg/kg, i.p.). Responses are demonstrated as area under the curve (AUC). #P < 0.001 and $P < 0.05 vs. Vehicle; *P < 0.001 and †P < 0.05 vs. OffCon using the Student t test (n = 6–8 per group, sex combined, mean ± SEM). (J) Mc4r mRNA in laser-dissected PVH normalized to the housekeeping genes β-actin and RPL13A (using the GeNorm program; n = 4–6 per group, sex combined). Means not sharing the same letter are significantly different from each other (P < 0.05) by generalized least squares (GLS) regression analysis. (K) α-MSH sensitivity curve with MAP response to MTII (y axis) vs. PVH Mc4r mRNA expression (x axis) in 6-mo-old OffCon (white)- vs. OffOb (black)-WT, -Mc4rKO, and -Mc4rPVH mice. OffOb showed a higher slope (P < 0.05) in the α-MSH sensitivity curve vs. OffCon [analysis of covariance (ANCOVA), n = 13].