P27 knockout mice: reduced myostatin in muscle and altered adipogenesis.
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.
Lin
Ji
J
Department of Animal & Dairy Science and Foods and Nutrition, University of Georgia, 444 Animal Science Complex, Athens, GA 30602-2771, USA.
Della-Fera
Mary Anne
MA
Li
Changlong
C
Page
Karen
K
Choi
Yang Ho
YH
Hartzell
Diane L
DL
Baile
Clifton A
CA
D000273:Adipose Tissue / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005838:Genotype; D020738:Leptin / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D055435:Myostatin; D009929:Organ Size; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D022763:CCAAT-Enhancer-Binding Protein-alpha; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D020738:Leptin; C525912:Mstn protein, mouse; D055435:Myostatin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27