TY - JOUR
T1 - Hedgehog signaling plays a conserved role in inhibiting fat formation
AU - Suh, Jae Myoung
AU - Gao, Xiaohuan
AU - McKay, Jim
AU - McKay, Renee
AU - Salo, Zack
AU - Graff, Jonathan M.
N1 - Funding Information:
We thank Drs. C. Dearolf, T. Furakawa, J. Jiang, A. McMahon, G. Nolan, B. Spiegelman, and D. Turner for reagents. We thank Drs. W. Dauer, M. Henkemeyer, M. Kyba, L. Parada, and R. Perlingeiro for helpful discussions. We thank members of the Graff lab for insights, help, and reagents. This work was supported by awards to J.M.G. from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). J.M.G. is an American Cancer Society Scholar and a Leukemia and Lymphoma Society Scholar.
PY - 2006/1
Y1 - 2006/1
N2 - Hedgehog (Hh) signals regulate invertebrate and vertebrate development, yet the role of the cascade in adipose development was undefined. To analyze a potential function, we turned to Drosophila and mammalian models. Fat-body-specific transgenic activation of Hh signaling inhibits fly fat formation. Conversely, fat-body-specific Hh blockade stimulated fly fat formation. In mammalian models, sufficiency and necessity tests showed that Hh signaling also inhibits mammalian adipogenesis. Hh signals elicit this function early in adipogenesis, upstream of PPARγ, potentially diverting preadipocytes as well as multipotent mesenchymal prescursors away from adipogenesis and toward osteogenesis. Hh may elicit these effects by inducing the expression of antiadipogenic transcription factors such as Gata2. These data support the notion that Hh signaling plays a conserved role, from invertebrates to vertebrates, in inhibiting fat formation and highlighting the potential of the Hh pathway as a therapeutic target for osteoporosis, lipodystrophy, diabetes, and obesity.
AB - Hedgehog (Hh) signals regulate invertebrate and vertebrate development, yet the role of the cascade in adipose development was undefined. To analyze a potential function, we turned to Drosophila and mammalian models. Fat-body-specific transgenic activation of Hh signaling inhibits fly fat formation. Conversely, fat-body-specific Hh blockade stimulated fly fat formation. In mammalian models, sufficiency and necessity tests showed that Hh signaling also inhibits mammalian adipogenesis. Hh signals elicit this function early in adipogenesis, upstream of PPARγ, potentially diverting preadipocytes as well as multipotent mesenchymal prescursors away from adipogenesis and toward osteogenesis. Hh may elicit these effects by inducing the expression of antiadipogenic transcription factors such as Gata2. These data support the notion that Hh signaling plays a conserved role, from invertebrates to vertebrates, in inhibiting fat formation and highlighting the potential of the Hh pathway as a therapeutic target for osteoporosis, lipodystrophy, diabetes, and obesity.
KW - Devbio
UR - http://www.scopus.com/inward/record.url?scp=33645046358&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645046358&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2005.11.012
DO - 10.1016/j.cmet.2005.11.012
M3 - Article
C2 - 16399502
AN - SCOPUS:33645046358
SN - 1550-4131
VL - 3
SP - 25
EP - 34
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -