(A–D) Diet-induced obese (DIO)-WT mice have increased levels of circulating leptin, food intake, and UCP-1 expression in brown fat and levels of urine norepinephrine, all suggestive of a state of leptin resistance (n = 8 per group).
(E and F) Increased baseline R, Rn, and AHR in DIO-WT mice reversed by leptin (Lep) ICV infusion (12 ng/hr for 5 days) (n = 8 per group, *DIO-WT versus DIO-WT Lep).
(G) Decreased endurance in DIO-WT mice reversed by leptin (Lep) ICV (12 ng/hr for 5 days) or inducible deletion of one allele of M3R in smooth muscle cells (M3RSM-ERT2+/−) (n = 8 per group).
(H) Bilateral cervical vagotomy causes a greater decrease in Rn in DIO-WT than in WT mice (n = 8 per group, arrow indicates time of vagotomy).
(I) High acetylcholine (Ach) levels in brain and lungs of DIO-WT mice corrected by leptin (Lep) ICV (12 ng/hr for 5 days) infusion (n = 6 per group).
(J) Decreased cholinesterase activity in DIO-WT improved by leptin ICV (n = 6 per group).
(K–M) Obese DIO-M3R+/− and DIO-M3RSM-ERT2+/− mice have baseline R, Rn, and AHR comparable to lean tamoxifen-treated SMCre-ERT2 and WT mice (n = 8 per group, *DIO-WT versus DIO-M3R+/−, #DIO-WT versus DIO-M3RSM-ERT2+/−).
For all panels, */#p < 0.05, **/##p < 0.01, and ***/###p < 0.001. Error bars represent the SEM. See also Figure S4.