Hedgehog signaling plays a conserved role in inhibiting fat formation.
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 PPARgamma, 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.
Suh
Jae Myoung
JM
Center for Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, NB5 118, Dallas, Texas 75390, USA.
Gao
Xiaohuan
X
McKay
Jim
J
McKay
Renee
R
Salo
Zack
Z
Graff
Jonathan M
JM
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D017124:Conserved Sequence; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000819:agonists / Q000502:physiology*; D004331:Drosophila melanogaster / Q000502:physiology; D019143:Evolution, Molecular; D005216:Fat Body / Q000502:physiology; D050980:GATA Transcription Factors / Q000502:physiology; D053823:Hedgehog Proteins / Q000819:agonists / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D039902:Multipotent Stem Cells / Q000502:physiology; D041681:NIH 3T3 Cells; D009765:Obesity / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D015415:Biomarkers; D029721:Drosophila Proteins; D050980:GATA Transcription Factors; D053823:Hedgehog Proteins; D047495:PPAR gamma; C077245:hh protein, Drosophila