The myostatin gene significantly increased muscle mass in both lean and obese (db/db) mice. A, Increased skeletal muscle mass by deletion of myostatin in both lean and obese (db/db) mice. B, Axial leg MRI scans. Muscle is shown in gray; adipose tissue is shown in white. C, Sections of distal hindlimbs (TA muscle) stained with hematoxylin and eosin (×200); bars represent 50 μm. A through C, left to right: lean, lean myostatin−/−, db/db, and db/db myostatin−/−. D, Tibialis anterior muscle weight of all groups of mice. E, Tibialis anterior myofiber diameter. Data reported here as representative hematoxylin and eosin–stained cryosections, and as box and whisker plots comprising minimum, median, and maximum value for myofiber diameter. Data are shown as mean±SEM (A through E: n=8). *P<0.05; ***P<0.001, lean myostatin−/− versus lean or db/db myostatin−/− versus db/db. #P<0.05; ##P<0.01, db/db versus lean or db/db myostatin−/− versus lean myostatin−/−. db/db myostatin−/− indicates mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐null mice heterozygous for leptin receptors; lean, lean dual heterozygotes; MRI, magnetic resonance imaging; TA, tibialis anterior.