The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Akt Stimulates Hepatic SREBP1c and Lipogenesis through Parallel mTORC1-Dependent and Independent Pathways
Open accessAbstract
Through unknown mechanisms, insulin activates the sterol regulatory element-binding protein (SREBP1c) transcription factor to promote hepatic lipogenesis. We find that this induction is dependent on the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). To further define the role of mTORC1 in the regulation of SREBP1c in the liver, we generated mice with liver-specific deletion of TSC1 (LTsc1KO), which results in insulin-independent activation of mTORC1. Surprisingly, the LTsc1KO mice are protected from age- and diet-induced hepatic steatosis and display hepatocyte-intrinsic defects in SREBP1c activation and de novo lipogenesis. These phenotypes result from attenuation of Akt signaling driven by mTORC1-dependent insulin resistance. Therefore, mTORC1 activation is not sufficient to stimulate hepatic SREBP1c in the absence of Akt signaling, revealing the existence of an additional downstream pathway also required for this induction. We provide evidence that this mTORC1-independent pathway involves Akt-mediated suppression of Insig2a, a liver-specific transcript encoding the SREBP1c inhibitor INSIG2.
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Cites
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SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
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SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
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Activation of a metabolic gene regulatory network downstream of mTOR complex 1
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Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
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Self-citationProtein Sensors for Membrane Sterols
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mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex
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Cited by
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
Hoxhaj, G., & Manning, B. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0216-7 · Cited by 2,137
Self-citationThe PI3K/AKT Pathway in Obesity and Type 2 Diabetes
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“AKT suppresses the expression of INSIG2A, a liver-specific transcript encoding the SREBP-1c inhibitor INSIG2, through an mTORC1-independent pathway [98].”
BackgroundReprogramming of fatty acid metabolism in cancer
Koundouros, N., & Poulogiannis, G. (2020) · British Journal of Cancer · doi:10.1038/s41416-019-0650-z · Cited by 1,614
SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology
Shimano, H., & Sato, R. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.91 · Cited by 1,174
Metadata
- Authors
- Yecies, J. L., Zhang, H. H., Menon, S., Liu, S., Yecies, D., Lipovsky, A. I., Gorgun, C., Kwiatkowski, D. J., Hotamisligil, G. S., Lee, C.-H., & Manning, B. D.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 14
- Issue
- 1
- Pages
- 21-32
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1998265194
- Cited by
- 657
- References
- 51
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 747 d)
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- Yecies, J. L., Zhang, H. H., Menon, S., Liu, S., Yecies, D., Lipovsky, A. I., Gorgun, C., Kwiatkowski, D. J., Hotamisligil, G. S., Lee, C.-H., & Manning, B. D. (2011). Akt Stimulates Hepatic SREBP1c and Lipogenesis through Parallel mTORC1-Dependent and Independent Pathways. Cell Metabolism. https://doi.org/10.1016/j.cmet.2011.06.002
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
