Changes after wheel running and daily irisin injection for 14 days. (a) Micro-CT 3D reconstruction of cortical bone (right femur), before and after. (b) The body weight loss percentage of control, F/I KO and F/I KO with the irisin injection group were 18 ± 0.58, 5.25 ± 1.25, and 14.3 ± 0.33, respectively (n = 5). (c) Serum irisin level after wheel running and injection for 14 days (n = 5). (d) Cort.BV/BS of the three groups before and after the exercise and injection. (e) Relative mRNA expression level of the genes related to white adipose tissue browning Cidea, Prdm16, Pgc‐1α and Ucp‐1 in white adipose tissue (inguinal fat) before and after the exercise and injection (n = 5). Values are shown as mean ± SD. CON, control; Cort.BV/BS, cortical bone surface/bone volume; F/I KO, Osx‐Cre:FNDC5/irisin KO mice; IRS INJ, irisin injection; KO, knockout; mRNA, messenger RNA; Pgc‐1α, peroxisome proliferator‐activated receptor‐γ coactivator 1α; Prdm16, PR domain‐containing 16; Ucp‐1, uncoupling protein 1. *p < .05, ***p < .001, ****p < .0001 versus control