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Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate

Authors :
UCL - MD/FARM - Ecole de pharmacie
Pospisilik, J. Andrew
Schramek, Daniel
Schnidar, Harald
Cronin, Shane J.F.
Nehme, Nadine T.
Zhang, Xiaoyun
Knauf, Claude
Cani, Patrice D.
Aumayr, Karin
Todoric, Jelena
Aberger, Fritz
Hiu, Chi-chung
Esterbauer, Harald
Penninger, Josef M.
Bayer, Martina
Haschemi, Arvand
Puviindran, Vijitha
Tar, Krisztina
Orthofer, Michael
Neely, G. Gregory
Dietzl, Georg
Manoukian, Armen
Funovics, Martin
Prager, Gerhard
Ferrandon, Dominique
UCL - MD/FARM - Ecole de pharmacie
Pospisilik, J. Andrew
Schramek, Daniel
Schnidar, Harald
Cronin, Shane J.F.
Nehme, Nadine T.
Zhang, Xiaoyun
Knauf, Claude
Cani, Patrice D.
Aumayr, Karin
Todoric, Jelena
Aberger, Fritz
Hiu, Chi-chung
Esterbauer, Harald
Penninger, Josef M.
Bayer, Martina
Haschemi, Arvand
Puviindran, Vijitha
Tar, Krisztina
Orthofer, Michael
Neely, G. Gregory
Dietzl, Georg
Manoukian, Armen
Funovics, Martin
Prager, Gerhard
Ferrandon, Dominique
Source :
Cell, Vol. 140, no. 1, p. 148-160 (2010)
Publication Year :
2010

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 similar to 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.

Details

Database :
OAIster
Journal :
Cell, Vol. 140, no. 1, p. 148-160 (2010)
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1130570483
Document Type :
Electronic Resource