The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
AMPK Phosphorylates and Inhibits SREBP Activity to Attenuate Hepatic Steatosis and Atherosclerosis in Diet-Induced Insulin-Resistant Mice
Open accessAbstract
Summary AMPK has emerged as a critical mechanism for salutary effects of polyphenols on lipid metabolic disorders in type 1 and type 2 diabetes. We demonstrate that AMPK interacts with and directly phosphorylates sterol regulatory element binding proteins (SREBP-1c and −2). Ser372 phosphorylation of SREBP-1c by AMPK is sufficient and necessary for inhibition of proteolytic processing and transcriptional activity of SREBP-1c in response to polyphenols and metformin. AMPK stimulates Ser372 phosphorylation, suppresses SREBP-1c cleavage and nuclear translocation, and represses SREBP-1c target gene expression in hepatocytes exposed to high glucose, leading to reduced lipogenesis and lipid accumulation. Hepatic activation of AMPK by the synthetic polyphenol S17834 protects against hepatic steatosis, hyperlipidemia, and accelerated atherosclerosis in diet-induced insulin resistant LDL receptor deficient mice in part through phosphorylation of SREBP-1c Ser372 and suppression of SREBP-1c and −2-dependent lipogenesis. AMPK-dependent phosphorylation of SREBP may offer novel therapeutic strategies to combat insulin resistance, dyslipidemia, and atherosclerosis.
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Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Self-citationResveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
Self-citationSREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Self-citationER Stress Induces Cleavage of Membrane-Bound ATF6 by the Same Proteases that Process SREBPs
Ye, J., Rawson, R. B., Komuro, R., Chen, X., Davé, U. P., Prywes, R., Brown, M. S., & Goldstein, J. L. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00133-7 · Cited by 1,871
Molecular mediators of hepatic steatosis and liver injury
Browning, J. D., & Horton, J. D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422422 · Cited by 1,772
SIRT1 Regulates Hepatocyte Lipid Metabolism through Activating AMP-activated Protein Kinase
Hou, X., Xu, S., Maitland-Toolan, K. A., Sato, K., Jiang, B., Ido, Y., Lan, F., Walsh, K., Wierzbicki, M., Verbeuren, T. J., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802187200 · Cited by 778
Self-citationUse of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation
Hawley, S. A., Ross, F. A., Chevtzoff, C., Green, K. A., Evans, A., Fogarty, S., Towler, M. C., Brown, L. J., Ogunbayo, O. A., Evans, A. M., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.04.001 · Cited by 773
Li, S., Brown, M. S., & Goldstein, J. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914798107 · Cited by 733 · cited 1×
“During the revision period, Goldstein and colleagues have reported that mTORC1 plays an essential role in regulating hyperinsulinemiainduced SREBP-1c and hepatic lipogenesis (Li et al., 2010).”
Insulin resistance and atherosclerosis
Semenkovich, C. F. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29024 · Cited by 481
Cited by
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
Self-citationMechanisms and regulation of cholesterol homeostasis
Luo, J., Yang, H., & Song, B.-L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0190-7 · Cited by 1,980
Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets
Gao, B., & Bataller, R. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.09.002 · Cited by 1,963
Self-citationCellular and molecular mechanisms of metformin: an overview
Viollet, B., Guigas, B., Garcia, N. S., Leclerc, J., Foretz, M., & Andreelli, F. (2012) · Clinical Science · doi:10.1042/cs20110386 · Cited by 1,720
Metadata
- Authors
- Li, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., Park, O., Luo, Z., Lefai, E., Shyy, J. Y.-J., Gao, B., Wierzbicki, M., Verbeuren, T. J., Shaw, R. J., Cohen, R. A., & Zang, M.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 13
- Issue
- 4
- Pages
- 376-388
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2011574523
- Cited by
- 1,778
- References
- 11
- FWCI
- 27.27
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Li, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., Park, O., Luo, Z., Lefai, E., Shyy, J. Y.-J., Gao, B., Wierzbicki, M., Verbeuren, T. J., Shaw, R. J., Cohen, R. A., & Zang, M. (2011). AMPK Phosphorylates and Inhibits SREBP Activity to Attenuate Hepatic Steatosis and Atherosclerosis in Diet-Induced Insulin-Resistant Mice. Cell Metabolism. https://doi.org/10.1016/j.cmet.2011.03.009
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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.
