Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin
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 gamma (PPARgamma) 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.
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Proteins of the retinoblastoma family and necdin selectively inhibit brown preadipocyte differentiation.
“Among the known inhibitors of preadipocyte-adipocyte transition, proteins of the retinoblastoma (Rb) family, and necdin, a growth repressor functionally resembling Rb, selectively inhibit brown preadipocyte differentiation 132,133,168”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [133]
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References 53 · Cited by 222
- Authors
- Tseng, Y.-H., Butte, A. J., Kokkotou, E., Yechoor, V. K., Taniguchi, C. M., Kriauciunas, K. M., Cypess, A. M., Niinobe, M., Yoshikawa, K., Patti, M. E., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Harvard University (US)
- Institute for Protein Research, The University of Osaka (JP)
- Corresponding author
- Kahn, C. Ronald
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2005-05-15
- Volume
- 7
- Issue
- 6
- Pages
- 601-611
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2077427931
- Cited by
- 222
- References
- 53
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 14 · 2019: 8 · 2018: 9 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 13 · 2013: 16 · 2012: 21
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 33201, DK63696, DK-60837, DK101183, K12DK063696, R01DK060837, R01DK033201, DK07260, T32DK007260, P30DK036836)
- U.S. National Library of Medicine (K22LM008261)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- adipogenesis, brown preadipocytes, insulin receptor substrate, NDN, preadipocyte factor-1, Wnt signaling, WNT10A, E2F4, PPARγ, CREB, insulin/IGF-1 signalling, gene expression profiling, brown adipogenesis
- MeSH terms
- Animals, Adipose Tissue, Brown, Calcium-Binding Proteins, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Membrane Proteins, Nerve Tissue Proteins, Nuclear Proteins, Receptor, Insulin, Repressor Proteins, Stem Cells, Transcription Factors, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Adipocytes, Mice, Knockout, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Intercellular Signaling Peptides and Proteins, PPAR gamma, E2F4 Transcription Factor, Wnt Proteins, Mice
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