1. Cell. 2010 Jan 8;140(1):148-160.

Drosophila Genome-wide Obesity Screen Reveals Hedgehog as a Determinant of Brown 
versus White Adipose Cell Fate.

Pospisilik JA, Schramek D, Schnidar H, Cronin SJ, Nehme NT, Zhang X, Knauf C,
Cani PD, Aumayr K, Todoric J, Bayer M, Haschemi A, Puviindran V, Tar K, Orthofer 
M, Neely GG, Dietzl G, Manoukian A, Funovics M, Prager G, Wagner O, Ferrandon D, 
Aberger F, Hui CC, Esterbauer H, Penninger JM.

Institute of Molecular Biotechnology of the Austrian Academy of Science, Dr.
Bohrgasse 3, A 1030 Vienna, Austria.

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. Copyright 
© 2010 Elsevier Inc. All rights reserved.

PMID: 20074523 [PubMed - as supplied by publisher]