Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice.
Myostatin (MSTN) is a secreted growth inhibitor expressed in muscle and adipose. We sought to determine whether expression of MSTN, its receptor activin RIIb (ActRIIb), or its binding protein follistatin-like-3 (FSTL3) are altered in subcutaneous or visceral adipose or in skeletal muscle in response to obesity. MSTN and ActRIIb mRNA levels were low in subcutaneous (SQF) and visceral fat (VF) from wild-type mice but were 50- to 100-fold higher in both SQF and VF from ob/ob compared with wild-type mice. FSTL3 mRNA levels were increased in SQF but decreased in VF in ob/ob compared with wild-type mice. Moreover, MSTN mRNA levels were twofold greater in tibialis anterior (TA) from ob/ob mice, whereas ActRIIb and FSTL3 mRNA levels were unchanged. MSTN mRNA levels were also increased in TA and SQF from mice on a high-fat diet. Injection of ob/ob mice with recombinant leptin caused FSTL3 mRNA levels to decrease in both VF and SQF in ob/ob mice; MSTN and ActRIIb mRNA levels tended to decrease only in VF. Finally, MSTN mRNA levels and promoter activity were low in adipogenic 3T3-L1 cells, but an MSTN promoter-reporter construct was activated in 3T3-L1 cells by cotransfection with the adipogenic transcription factors SREBP-1c, C/EBPalpha, and PPARgamma. These results demonstrate that expression of MSTN and its associated binding proteins can be modulated in adipose tissue and skeletal muscle by chronic obesity and suggest that alterations in their expression may contribute to the changes in growth and metabolism of lean and fat tissues occurring during obesity.
Allen
David L
DL
Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO, USA. allendl@colorado.edu
Cleary
Allison S
AS
Speaker
Kristin J
KJ
Lindsay
Sarah F
SF
Uyenishi
Jill
J
Reed
Jason M
JM
Madden
Molly C
MC
Mehan
Ryan S
RS
D016475:3T3 Cells; D030301:Activin Receptors, Type II / Q000096:biosynthesis* / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D038702:Follistatin-Related Proteins; D020738:Leptin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism*; D055435:Myostatin; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics*
D004041:Dietary Fats; D038702:Follistatin-Related Proteins; C498620:Fstl3 protein, mouse; D020738:Leptin; C525912:Mstn protein, mouse; D055435:Myostatin; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B