Reference Report

Reference
Citation	Pospisilik, J.A., Schramek, D., Schnidar, H., Cronin, S.J., Nehme, N.T., Zhang, X., Knauf, C., Cani, P.D., Aumayr, K., Todoric, J., Bayer, M., Haschemi, A., Puviindran, V., Tar, K., Orthofer, M., Neely, G.G., Dietzl, G., Manoukian, A., Funovics, M., Prager, G., Wagner, O., Ferrandon, D., Aberger, F., Hui, C.C., Esterbauer, H., Penninger, J.M. (2010). Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate. Cell 140(1): 148--160. (Export to RIS)
FlyBase ID	FBrf0212676
Publication Type	Research paper
PubMed ID	20074523
PubMed Abstract	Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Cell
Title	Cell
Publication Year	1974-
ISBN/ISSN	0092-8674
Data from Reference
Alleles (6)
	Scer\GAL4^C57 Scer\GAL4^hs.PB Scer\GAL4^n-syb.PS Scer\GAL4^OK72 Scer\GAL4^ppl.PP Scer\GAL80^ts.αTub84B
Constructs (4)
	P{GAL4-Hsp70.PB} P{n-syb-GAL4.S} P{ppl-GAL4.P} P{tubP-GAL80^ts}
Genes (94)
	adp Akh AkhR Ant2 Apc2 bgm CG1516 CG1572 CG2852 CG3213 CG5550 CG6788 CG8239 CG8257 CG8451 CG8534 CG8665 CG9399 CG9485 CG10407 CG12691 CG15169 CG18563 CG30271 CG31172 CG31219 CG31697 CG32442 CG34398 CG34404 CG43342 CG43343 ci CkIα Crtc Cyp6a2 desat1 DopR2 fbp Fur1 Gpo-1 Gr36b Gr98b hh HLH106 hyd ihog Ilp2 Ilp3 Ilp5 IM10 InR Lpt Lsd-1 Lsd-2 mirr mtacp1 MtnA nej Nf-YC Nmda1 oa2 Obp56a Obp83cd Oct-TyrR opm Or10a Or56a Or65a Or67a P5cr Pi3K21B Pi3K59F Pi3K68D Pi3K92E ppk23 qin Rfabg S6kII Scer\GAL4 Scer\GAL80 shtd slmb Smg5 smo ste24c Su(fu) sws Sxl T3dh trr Tsc1 ttv Usp7
Insertions (2)
	P{GawB}C57 P{GawB}OK72