Knockout of the P27(kip) gene, which encodes a cyclin-dependent kinase inhibitor involved in cell proliferation regulation, results in growth enhancement in mice. To investigate how p27 deficiency affected adipogenesis and myogenesis, levels of PPARgamma, C/EBPalpha, and the myogenesis inhibitor, myostatin, were measured in p27(-/-) (n = 14), p27(+/-) (n = 18). and p27(+/+) mice (n = 11). Body weight and gastrocnemius muscle (GC) mass were increased in p27(-/-) mice (P < 0.05), but there were no differences in fat depot weights, percent body fat or serum leptin concentrations among genotypes. PPARgamma but not C/EBPalpha, was markedly increased in p27(-/-) mice (P < 0.05). There was also a higher incidence of inguinal fat apoptosis (P < 0.01) in p27(-/-) mice. Myostatin levels were reduced in GC muscle of p27(-/-) mice (P < 0.05). These findings suggest that in p27 deficient mice, increased skeletal muscle mass is mediated in part through decreased myostatin. Although total adiposity was not changed, increased PPARgamma levels suggest an alteration in adipogenesis. (C) 2002 Elsevier Science (USA). All rights reserved.