A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism

Nature Communications

Volumn 6, Issue , 2015, Pages

  Xu, Yang ^a   Zalzala, Munaf ^a   Xu, Jiesi ^a   Li, Yuanyuan ^a   Yin, Liya ^a   Zhang, Yanqiao ^a  

^a Northeastern Ohio Medical University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEPATOCYTE NUCLEAR FACTOR 4ALPHA; MICRORNA 34A; APOLIPOPROTEIN E; HEPATOCYTE NUCLEAR FACTOR 4; HNF4A PROTEIN, HUMAN; HNF4A PROTEIN, MOUSE; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; MICRORNA; MIRN34 MICRORNA, HUMAN; MIRN34 MICRORNA, MOUSE; TRIACYLGLYCEROL;

GENE EXPRESSION; HORMONE; LIPID; METABOLISM; PATHOGENICITY; PROTEIN; RODENT; SECRETION;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATHEROSCLEROSIS; CONTROLLED STUDY; DIABETES MELLITUS; DISEASE COURSE; FEMALE; HUMAN; HUMAN TISSUE; HYPOLIPEMIA; LIPID METABOLISM; LIPOPROTEIN BLOOD LEVEL; LIPOPROTEIN METABOLISM; LIVER CELL; MALE; METABOLIC STRESS; MOUSE; NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOGENESIS; PROTEIN EXPRESSION; ANIMAL; EXPERIMENTAL DIABETES MELLITUS; GENETICS; HEP-G2 CELL LINE; KNOCKOUT MOUSE; LIVER; METABOLISM; MIDDLE AGED; PHYSIOLOGICAL STRESS;

MURINAE; MUS;

ANIMALS; APOLIPOPROTEINS E; ATHEROSCLEROSIS; DIABETES MELLITUS, EXPERIMENTAL; HEP G2 CELLS; HEPATOCYTE NUCLEAR FACTOR 4; HUMANS; LIPID METABOLISM; LIPOPROTEINS; LIVER; MICE, KNOCKOUT; MICRORNAS; MIDDLE AGED; NON-ALCOHOLIC FATTY LIVER DISEASE; RECEPTORS, LDL; STRESS, PHYSIOLOGICAL; TRIGLYCERIDES;

EID: 84935009342     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms8466     Document Type: Article

References (46)

1. Petersen, K. F. et al. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 54, 603-608 (2005).
2. Yki-Jarvinen, H. Fat in the liver and insulin resistance. Ann. Med. 37, 347-356 (2005).
3. Anstee, Q. M., Goldin, R. D. Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int. J. Exp. Pathol. 87, 1-16 (2006).
4. Angulo, P. Nonalcoholic fatty liver disease. N. Engl. J. Med. 346, 1221-1231 (2002).
5. Li, Y., Jadhav, K., Zhang, Y. Bile acid receptors in non-alcoholic fatty liver disease. Biochem. Pharmacol. 86, 1517-1524 (2013).
6. Day, C. P., James, O. F. Steatohepatitis: a tale of two 'hits'? Gastroenterology 114, 842-845 (1998).
7. Farrell, G. C., Larter, C. Z. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43, S99-S112 (2006).
8. Angulo, P. Treatment of nonalcoholic fatty liver disease. Ann. Hepatol. 1, 12-19 (2002).
9. Lewis, J. R., Mohanty, S. R. Nonalcoholic fatty liver disease: a review and update. Dig. Dis. Sci. 55, 560-578 (2010).
10. Drewes, T., Senkel, S., Holewa, B., Ryffel, G. U. Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. Mol. Cell Biol. 16, 925-931 (1996).
11. Jiang, S. et al. Expression and localization of P1 promoter-driven hepatocyte nuclear factor-4alpha (HNF4alpha) isoforms in human and rats. Nucl. Recept. 1, 5 (2003).
12. Dhe-Paganon, S., Duda, K., Iwamoto, M., Chi, Y. I., Shoelson, S. E. Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand. J. Biol. Chem. 277, 37973-37976 (2002).
13. Wisely, G. B. et al. Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure 10, 1225-1234 (2002).
14. Fajans, S. S., Bell, G. I., Polonsky, K. S. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N. Engl. J. Med. 345, 971-980 (2001).
15. Miura, A. et al. Hepatocyte nuclear factor-4alpha is essential for glucosestimulated insulin secretion by pancreatic beta-cells. J. Biol. Chem. 281, 5246-5257 (2006).
16. Lehto, M. et al. Mutation in the HNF-4alpha gene affects insulin secretion and triglyceride metabolism. Diabetes 48, 423-425 (1999).
17. Shih, D. Q. et al. Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels. Diabetes 49, 832-837 (2000).
18. Pramfalk, C. et al. Control of ACAT2 liver expression by HNF4{alpha}: lesson from MODY1 patients. Arterioscler. Thromb. Vasc. Biol. 29, 1235-1241 (2009).
19. Yin, L., Ma, H., Ge, X., Edwards, P. A., Zhang, Y. Hepatic hepatocyte nuclear factor 4alpha is essential for maintaining triglyceride and cholesterol homeostasis. Arterioscler. Thromb. Vasc. Biol. 31, 328-336 (2011).
20. Hayhurst, G. P., Lee, Y. H., Lambert, G., Ward, J. M., Gonzalez, F. J. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol. Cell Biol. 21, 1393-1403 (2001).
21. Fernandez-Hernando, C., Suarez, Y., Rayner, K. J., Moore, K. J. MicroRNAs in lipid metabolism. Curr. Opin. Lipidol. 22, 86-92 (2011).
22. Sacco, J., Adeli, K. MicroRNAs: emerging roles in lipid and lipoprotein metabolism. Curr. Opin. Lipidol. 23, 220-225 (2012).
23. Soh, J., Iqbal, J., Queiroz, J., Fernandez-Hernando, C., Hussain, M. M. MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Nat. Med. 19, 892-900 (2013).
24. Cheung, O., Sanyal, A. J. Role of microRNAs in non-alcoholic steatohepatitis. Curr. Pharm. Des. 16, 1952-1957 (2010).
25. Rottiers, V., Naar, A. M. MicroRNAs in metabolism and metabolic disorders. Nat. Rev. Mol. Cell Biol. 13, 239-250 (2012).
26. Raver-Shapira, N. et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol. Cell 26, 731-743 (2007).
27. Chang, T. C. et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell 26, 745-752 (2007).
28. Tarasov, V. et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6, 1586-1593 (2007).
29. He, L. et al. A microRNA component of the p53 tumour suppressor network. Nature 447, 1130-1134 (2007).
30. Derdak, Z. et al. Inhibition of p53 attenuates steatosis and liver injury in a mouse model of non-alcoholic fatty liver disease. J. Hepatol. 58, 785-791 (2013).
31. Yahagi, N. et al. p53 involvement in the pathogenesis of fatty liver disease. J. Biol. Chem. 279, 20571-20575 (2004).
32. Inoue, Y., Hayhurst, G. P., Inoue, J., Mori, M., Gonzalez, F. J. Defective ureagenesis in mice carrying a liver-specific disruption of hepatocyte nuclear factor 4alpha (HNF4alpha ). HNF4alpha regulates ornithine transcarbamylase in vivo. J. Biol. Chem. 277, 25257-25265 (2002).
33. Cheung, O. et al. Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression. Hepatology 48, 1810-1820 (2008).
34. Cermelli, S., Ruggieri, A., Marrero, J. A., Ioannou, G. N., Beretta, L. Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PloS ONE 6, e23937 (2011).
35. Lee, J. et al. A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition. J. Biol. Chem. 285, 12604-12611 (2010).
36. Trajkovski, M. et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature 474, 649-653 (2011).
37. Lamba, V., Ghodke, Y., Guan, W., Tracy, T. S. microRNA-34a is associated with expression of key hepatic transcription factors and cytochromes P450. Biochem. Biophys. Res. Commun. 445, 404-411 (2014).
38. Choi, S. E. et al. Elevated microRNA-34a in obesity reduces NAD\+ levels and SIRT1 activity by directly targeting NAMPT. Aging Cell 12, 1062-1072 (2013).
39. Charlton, M., Sreekumar, R., Rasmussen, D., Lindor, K., Nair, K. S. Apolipoprotein synthesis in nonalcoholic steatohepatitis. Hepatology 35, 898-904 (2002).
40. Ge, X. et al. Aldo-keto reductase 1B7 is a target gene of FXR and regulates lipid and glucose homeostasis. J. Lipid Res. 52, 1561-1568 (2011).
41. Zhang, Y. et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc. Natl Acad. Sci. USA 103, 1006-1011 (2006).
42. Zhang, Y., Yin, L., Hillgartner, F. B. SREBP-1 integrates the actions of thyroid hormone, insulin, cAMP, and medium-chain fatty acids on ACCalpha transcription in hepatocytes. J. Lipid Res. 44, 356-368 (2003).
43. Bligh, E. G., Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911-917 (1959).
44. Xu, J. et al. Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis. Hepatology 59, 1761-1771 (2014).
45. Zhang, Y. et al. FXR deficiency causes reduced atherosclerosis in Ldlr-/-mice. Arterioscler. Thromb. Vasc. Biol. 26, 2316-2321 (2006).
46. Zhang, Y. et al. Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice. Mol. Endocrinol. 26, 272-280 (2012).