(A) Representative images of immunofluorescence staining of colocalization of Osterix (red) and osteocalcin (red) with YFP (green) (representing LepR+ cells) and (B, C) quantitative analysis of (B) YFP+ osterix+ cells per section and (C) YFP+ osteoblasts per section in femur bone marrow from 3-month-old Lepr;YFP mice treated with propranolol (0.5 mg/kg/day for 6 weeks), 5 μmol/mouse/day [Leu31, Pro34]-NPY, and a combination of propranolol (0.5 mg/kg/d for 6 weeks) and 5 umol/mouse/d [Leu31, Pro34]-NPY for 4 weeks. Scale bars = 50 µm. (D) Representative images of alizarin red S–stained CFU-Ob and crystal violet–stained CFU-F. Quantitative analysis of (E) CFU-Ob and (F) CFU-F MSCs isolated from 3-month-old male Lepr;YFP mice treated with propranolol (0.5 mg/kg/d for 6 weeks), 5 umol/mouse/day [Leu31, Pro34]-NPY, and a combination of propranolol (0.5 mg/kg/day for 6 weeks) and 5 umol/mouse/d [Leu31, Pro34]-NPY for 4 weeks. N ≥ six per group. *p < 0.05 and N.S. indicates not significant. Statistical significance was determined by two-way analysis of variance. (G) Diagram showing that PGE2/EP4 ascending signal also downregulates expression of neuroendocrine factor NPY, which is secreted into circulation, as the neuroendocrine descending interoceptive signal for bone and fat metabolism.