Article abstract
Nature Cell Biology 7, 601 - 611 (2005)
Published online: 15 May 2005 | doi:10.1038/ncb1259
Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin
Yu-Hua Tseng1,5, Atul J. Butte2,4,5, Efi Kokkotou1, Vijay K. Yechoor1, Cullen M. Taniguchi1, Kristina M. Kriauciunas1, Aaron M. Cypess1, Michio Niinobe3, Kazuaki Yoshikawa3, Mary Elizabeth Patti1 & C. Ronald Kahn1
Abstract
The insulin/IGF-1 (insulin-like growth factor 1) signalling pathway promotes adipocyte differentiation via complex signalling networks. Here, using microarray analysis of brown preadipocytes that are derived from wild-type and insulin receptor substrate (Irs) knockout animals that exhibit progressively impaired differentiation, we define 374 genes/expressed-sequence tags whose expression in preadipocytes correlates with the ultimate ability of the cells to differentiate. Many of these genes, including preadipocyte factor-1 (Pref-1) and multiple members of the Wnt signalling pathway, are related to early adipogenic events. Necdin is also markedly increased in Irs knockout cells that cannot differentiate, and knockdown of necdin restores brown adipogenesis with downregulation of Pref-1 and Wnt10a expression. Insulin receptor substrate proteins regulate a necdin–E2F4 interaction that represses peroxisome-proliferator-activated receptor 
(PPAR) transcription via a cyclic AMP response element binding protein (CREB)-dependent pathway. Together these define a key signalling network that is involved in brown preadipocyte determination.
- Research Division, Joslin Diabetes Center, Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.
- Informatics Program, Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.
- Division of Regulation of Macromolecular Function, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
- Present address: Stanford Medical Informatics, 251 Campus Drive, Room X-215, Stanford, CA 94305-5479, USA.
- These authors contributed equally to this work.
Correspondence to: C. Ronald Kahn1 e-mail: c.ronald.kahn@joslin.harvard.edu
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