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The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Ablation of gp78 in Liver Improves Hyperlipidemia and Insulin Resistance by Inhibiting SREBP to Decrease Lipid Biosynthesis

Liu, Tong-Fei, Tang, Jing-Jie, Li, Pei-Shan, Shen, Yang, Li, Jia-Gui, Miao, Hong-Hua, Li, Bo-Liang, Song, Bao-Liang·2012·Cell Metabolism
DOI 10.1016/j.cmet.2012.06.014
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Abstract

gp78 is a membrane-anchored ubiquitin ligase mediating the degradation of HMG-CoA reductase (HMGCR) and Insig-1. As a rate-limiting enzyme in cholesterol biosynthesis, HMGCR undergoes rapid sterol-promoted degradation. In contrast, destruction of Insig-1 releases its inhibition on SREBP and stimulates the expression of lipogenic genes. Thus, gp78 has opposite effects on lipid biosynthesis. We here generated liver-specific gp78 knockout (L-gp78(-/-)) mice and showed that although the degradation of HMGCR was blunted, SREBP was suppressed due to the elevation of Insig-1/-2, and therefore the lipid biosynthesis was decreased. The L-gp78(-/-) mice were protected from diet-/age-induced obesity and glucose intolerance. The livers of L-gp78(-/-) mice produced more FGF21, which activated thermogenesis in brown adipocytes and enhanced energy expenditure. Together, the major function of gp78 in liver is regulating lipid biosynthesis through SREBP pathway. Ablation of gp78 decreases the lipid levels and increases FGF21, and is beneficial to patients with metabolic diseases.

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Crossref · 10.1016/j.cmet.2012.06.014

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Research works printed but not linked: 31

  1. Badman, 2007, Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states, Cell Metab., 5, 426, 10.1016/j.cmet.2007.05.002 · DOI · Paper page
  2. Brown, 1979, Active and inactive forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver of the rat. Comparison with the rate of cholesterol synthesis in different physiological states, J. Biol. Chem., 254, 5144, 10.1016/S0021-9258(18)50571-8 · DOI
  3. Cao, 2007, Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase, Cell Metab., 6, 115, 10.1016/j.cmet.2007.07.002 · DOI
  4. DeBose-Boyd, 2008, Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase, Cell Res., 18, 609, 10.1038/cr.2008.61 · DOI · Paper page
  5. Engelking, 2004, Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis, J. Clin. Invest., 113, 1168, 10.1172/JCI20978 · DOI · Paper page
  6. Goldstein, 2006, Protein sensors for membrane sterols, Cell, 124, 35, 10.1016/j.cell.2005.12.022 · DOI · Paper page
  7. Gong, 2006, Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake, Cell Metab., 3, 15, 10.1016/j.cmet.2005.11.014 · DOI · Paper page
  8. Inagaki, 2007, Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21, Cell Metab., 5, 415, 10.1016/j.cmet.2007.05.003 · DOI · Paper page
  9. Janowski, 1996, An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha, Nature, 383, 728, 10.1038/383728a0 · DOI · Paper page
  10. Kharitonenkov, 2011, FGF21 reloaded: challenges of a rapidly growing field, Trends Endocrinol. Metab., 22, 81, 10.1016/j.tem.2010.11.003 · DOI
  11. Kita, 1980, Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in livers of mice treated with mevinolin, a competitive inhibitor of the reductase, J. Clin. Invest., 66, 1094, 10.1172/JCI109938 · DOI
  12. Kuriyama, 2005, Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver, Cell Metab., 1, 41, 10.1016/j.cmet.2004.11.004 · DOI
  13. Lee, 2006, Proteasomal degradation of ubiquitinated Insig proteins is determined by serine residues flanking ubiquitinated lysines, Proc. Natl. Acad. Sci. USA, 103, 4958, 10.1073/pnas.0600422103 · DOI
  14. Lee, 2006, Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78, J. Biol. Chem., 281, 39308, 10.1074/jbc.M608999200 · DOI
  15. Lopez, 2008, PCSK9: an enigmatic protease, Biochim. Biophys. Acta, 1781, 184, 10.1016/j.bbalip.2008.01.003 · DOI
  16. Obregon, 2008, Thyroid hormone and adipocyte differentiation, Thyroid, 18, 185, 10.1089/thy.2007.0254 · DOI
  17. Robidoux, 2004, Beta-adrenergic receptors and regulation of energy expenditure: a family affair, Annu. Rev. Pharmacol. Toxicol., 44, 297, 10.1146/annurev.pharmtox.44.101802.121659 · DOI
  18. Sellayah, 2011, Orexin is required for brown adipose tissue development, differentiation, and function, Cell Metab., 14, 478, 10.1016/j.cmet.2011.08.010 · DOI · Paper page
  19. Shimano, 1997, Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene, J. Clin. Invest., 100, 2115, 10.1172/JCI119746 · DOI · Paper page
  20. Song, 2005, Insig-mediated degradation of HMG CoA reductase stimulated by lanosterol, an intermediate in the synthesis of cholesterol, Cell Metab., 1, 179, 10.1016/j.cmet.2005.01.001 · DOI
  21. Song, 2005, Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase, Mol. Cell, 19, 829, 10.1016/j.molcel.2005.08.009 · DOI · Paper page
  22. St. Pierre, 2011, The Gp78 ubiquitin ligase: probing endoplasmic reticulum complexity, Protoplasma, 249, S11
  23. Tang, 2011, Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques, Cell Metab., 13, 44, 10.1016/j.cmet.2010.12.004 · DOI · Paper page
  24. Tschop, 2012, A guide to analysis of mouse energy metabolism, Nat. Methods, 9, 57, 10.1038/nmeth.1806 · DOI · Paper page
  25. Tseng, 2008, New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure, Nature, 454, 1000, 10.1038/nature07221 · DOI · Paper page
  26. Yabe, 2002, Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins, Proc. Natl. Acad. Sci. USA, 99, 12753, 10.1073/pnas.162488899 · DOI · Paper page
  27. Yabe, 2003, Liver-specific mRNA for Insig-2 down-regulated by insulin: implications for fatty acid synthesis, Proc. Natl. Acad. Sci. USA, 100, 3155, 10.1073/pnas.0130116100 · DOI
  28. Yahagi, 2002, Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice, J. Biol. Chem., 277, 19353, 10.1074/jbc.M201584200 · DOI
  29. Yang, 2002, Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER, Cell, 110, 489, 10.1016/S0092-8674(02)00872-3 · DOI · Paper page
  30. Zelcer, 2009, LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor, Science, 325, 100, 10.1126/science.1168974 · DOI · Paper page
  31. Zhang, 2011, The link between fibroblast growth factor 21 and sterol regulatory element binding protein 1c during lipogenesis in hepatocytes, Mol. Cell. Endocrinol., 342, 41, 10.1016/j.mce.2011.05.003 · DOI

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Metadata

Authors
Liu, T.-F., Tang, J.-J., Li, P.-S., Shen, Y., Li, J.-G., Miao, H.-H., Li, B.-L., & Song, B.-L.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2012-08
Volume
16
Issue
2
Pages
213-225
ISSN
1550-4131
DOI
10.1016/j.cmet.2012.06.014
Cited by
127
References
7
Language
en
Licence

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