Iron Metabolism in Nonalcoholic Fatty Liver Disease

Overview

Journal Curr Gastroenterol Rep

Specialty Gastroenterology

Date 2011 Nov 30

PMID 22124850

Citations 55

Authors

James E Nelson

Heather Klintworth

Kris V Kowdley

Affiliations

Soon will be listed here.

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common worldwide clinical and major public health problem affecting both adults and children in developed nations. Increased hepatic iron stores are observed in about one-third of adult NAFLD patients. Iron deposition may occur in parenchymal and/or non-parenchymal cells of the reticuloendothelial system (RES). Similar patterns of iron deposition have been associated with increased severity of other chronic liver diseases including HCV infection and dysmetabolic iron overload, suggesting there may be a common mechanism for hepatic iron deposition in these diseases. In NAFLD, iron may potentiate the onset and progression of disease by increasing oxidative stress and altering insulin signaling and lipid metabolism. The impact of iron in these processes may depend upon the sub-cellular location of iron deposition in hepatocytes or RES cells. Iron depletion therapy has shown efficacy at reducing serum aminotransferase levels and improving insulin sensitivity in subjects with NAFLD.

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References

Tsukamoto H . Iron regulation of hepatic macrophage TNFalpha expression. Free Radic Biol Med. 2002; 32(4):309-13. DOI: 10.1016/s0891-5849(01)00772-9. View

Barisani D, Pelucchi S, Mariani R, Galimberti S, Trombini P, Fumagalli D . Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload. J Hepatol. 2008; 49(1):123-33. DOI: 10.1016/j.jhep.2008.03.011. View

Chitturi S, Weltman M, Farrell G, McDonald D, Kench J, Liddle C . HFE mutations, hepatic iron, and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. Hepatology. 2002; 36(1):142-9. DOI: 10.1053/jhep.2002.33892. View

Sumida Y, Kanemasa K, Fukumoto K, Yoshida N, Sakai K, Nakashima T . Effect of iron reduction by phlebotomy in Japanese patients with nonalcoholic steatohepatitis: A pilot study. Hepatol Res. 2006; 36(4):315-21. DOI: 10.1016/j.hepres.2006.08.003. View

Goswami T, Andrews N . Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem. 2006; 281(39):28494-8. DOI: 10.1074/jbc.C600197200. View

Duseja A, Das R, Nanda M, Das A, Garewal G, Chawla Y . Nonalcoholic steatohepatitis in Asian Indians is neither associated with iron overload nor with HFE gene mutations. World J Gastroenterol. 2005; 11(3):393-5. PMC: 4205345. DOI: 10.3748/wjg.v11.i3.393. View

Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B . Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology. 2006; 131(3):788-96. DOI: 10.1053/j.gastro.2006.07.007. View

Ganz T . Hepcidin--a regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract Res Clin Haematol. 2005; 18(2):171-82. DOI: 10.1016/j.beha.2004.08.020. View

Hanada T, Yoshimura A . Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev. 2002; 13(4-5):413-21. DOI: 10.1016/s1359-6101(02)00026-6. View

10.

Tsukamoto H, Rippe R, Niemela O, Lin M . Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibrogenesis. J Gastroenterol Hepatol. 1995; 10 Suppl 1:S50-3. DOI: 10.1111/j.1440-1746.1995.tb01798.x. View

11.

Graham R, Chua A, Carter K, Delima R, Johnstone D, Herbison C . Hepatic iron loading in mice increases cholesterol biosynthesis. Hepatology. 2010; 52(2):462-71. DOI: 10.1002/hep.23712. View

12.

Valenti L, Moscatiello S, Vanni E, Fracanzani A, Bugianesi E, Fargion S . Venesection for non-alcoholic fatty liver disease unresponsive to lifestyle counselling--a propensity score-adjusted observational study. QJM. 2010; 104(2):141-9. DOI: 10.1093/qjmed/hcq170. View

13.

Friedman S . Mechanisms of hepatic fibrogenesis. Gastroenterology. 2008; 134(6):1655-69. PMC: 2888539. DOI: 10.1053/j.gastro.2008.03.003. View

14.

Nakashima T, Sumida Y, Furutani M, Hirohama A, Okita M, Mitsuyoshi H . Elevation of serum thioredoxin levels in patients with nonalcoholic steatohepatitis. Hepatol Res. 2005; 33(2):135-7. DOI: 10.1016/j.hepres.2005.09.021. View

15.

Pietrangelo A . Metals, oxidative stress, and hepatic fibrogenesis. Semin Liver Dis. 1996; 16(1):13-30. DOI: 10.1055/s-2007-1007215. View

16.

Bonkovsky H, Lambrecht R, Shan Y . Iron as a co-morbid factor in nonhemochromatotic liver disease. Alcohol. 2003; 30(2):137-44. DOI: 10.1016/s0741-8329(03)00127-7. View

17.

Xiong S, She H, Sung C, Tsukamoto H . Iron-dependent activation of NF-kappaB in Kupffer cells: a priming mechanism for alcoholic liver disease. Alcohol. 2003; 30(2):107-13. DOI: 10.1016/s0741-8329(03)00100-9. View

18.

Pietrangelo A . The penetrance of hemochromatosis: mice to the rescue. Gastroenterology. 2007; 132(2):805-8. DOI: 10.1053/j.gastro.2007.01.011. View

19.

Oliveira S, Pinto J, Picarote G, Costa V, Carvalho F, Rangel M . ER stress-inducible factor CHOP affects the expression of hepcidin by modulating C/EBPalpha activity. PLoS One. 2009; 4(8):e6618. PMC: 2719873. DOI: 10.1371/journal.pone.0006618. View

20.

Kirsch R, Sijtsema H, Tlali M, Marais A, Hall P . Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease. Liver Int. 2006; 26(10):1258-67. DOI: 10.1111/j.1478-3231.2006.01329.x. View