Myostatin knockout in mice increases myogenesis and decreases adipogenesis.
Growth differentiation factor-8 (GDF-8), or Myostatin, plays an important inhibitory role during muscle development. Since muscle and adipose tissue develop from the same mesenchymal stem cells, we hypothesized that Myostatin gene knockout may cause a switch between myogenesis and adipogenesis. Male and female wild type (WT) and Myostatin knockout (KO) mice were sacrificed at 4, 8, and 12 weeks of age. The gluteus muscle (GM) was larger in KO mice compared to WT mice at 8 (P < 0.01) and 12 (P < 0.001) weeks. At 12 weeks, KO mice had decreased fat depots (P < 0.01). Compared to 12-week-old WT mice, serum leptin concentration in KO mice was lower (P < 0.001) and leptin mRNA expression was decreased (P < 0.01) in inguinal adipose tissue. CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor-gamma (PPARgamma) levels in adipose tissue were significantly lower in KO mice compared to WT mice. Thus, increased muscle development in Myostatin knockout mice is associated with reduced adipogenesis and consequently, decreased leptin secretion.
Lin
Ji
J
Animal & Dairy Science Department, University of Georgia, Athens, Georgia 30602-2771, USA.
Arnold
Heather B
HB
Della-Fera
Mary Anne
MA
Azain
Michael J
MJ
Hartzell
Diane L
DL
Baile
Clifton A
CA
D000273:Adipose Tissue / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000032:analysis; D004435:Eating; D005260:Female; D007700:Kinetics; D020738:Leptin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D055435:Myostatin; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D020738:Leptin; C525912:Mstn protein, mouse; D055435:Myostatin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D016212:Transforming Growth Factor beta