The Potential Role of Iron and Copper in Pediatric Obesity and Nonalcoholic Fatty Liver Disease

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2015 Aug 15

PMID 26273604

Citations 18

Authors

Alexandra Feldman

Elmar Aigner

Daniel Weghuber

Katharina Paulmichl

Affiliations

Soon will be listed here.

Abstract

Obesity is a rapidly growing health problem and is paralleled by a multitude of comorbidities, including nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common chronic liver disease in both adults and children. The current understanding of NAFLD is still fragmentary. While simple steatosis is characterized by the interplay between excessive free fatty acid accumulation and hepatic insulin resistance, the progression to NASH has been related to oxidative stress and a proinflammatory state with dysbalanced adipokine, cytokine levels, and endotoxin-mediated immune response. In addition, oxidative stress has been suggested to play a central role for the sequelae leading to NASH. Trace elements are critical in regulatory, immunologic, and antioxidant functions resulting in protection against inflammation and peroxidation and consequently against the known comorbidities of obesity. Disruptions of the metal detoxification processes located in the liver are plausibly related to NAFLD development via oxidative stress. Perturbations of iron and copper (Cu) homeostasis have been shown to contribute to the pathogenesis of NAFLD. This review presents current data from pediatric studies. In addition, data from adult studies are summarized where clinical relevance may be extrapolated to pediatric obesity and NAFLD.

Citing Articles

Cuproptosis Cell Death Molecular Events and Pathways to Liver Disease.

Mao Y, Chen H, Zhu W, Ni S, Luo S, Tang S J Inflamm Res. 2025; 18:883-894.

PMID: 39867947 PMC: 11760270. DOI: 10.2147/JIR.S498340.

Overweight, Obesity, Hypertriglyceridemia, and Insulin Resistance Are Positively Associated with High Serum Copper Levels in Mexican Adults.

Ramirez-Cruz A, Rios-Lugo M, Soto-Sanchez J, Juarez-Perez C, Cabello-Lopez A, Jimenez-Ramirez C Metabolites. 2024; 14(5).

PMID: 38786759 PMC: 11122773. DOI: 10.3390/metabo14050282.

Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway.

Jiang T, Xiao Y, Zhou J, Luo Z, Yu L, Liao Q Redox Biol. 2023; 68:102963.

PMID: 37984229 PMC: 10694775. DOI: 10.1016/j.redox.2023.102963.

Micronutrient Deficiency in Children and Adolescents with Obesity-A Narrative Review.

Calcaterra V, Verduci E, Milanta C, Agostinelli M, Todisco C, Bona F Children (Basel). 2023; 10(4).

PMID: 37189944 PMC: 10136772. DOI: 10.3390/children10040695.

Recent advances in the application of ionomics in metabolic diseases.

Zhang Y, Huang B, Jin J, Xiao Y, Ying H Front Nutr. 2023; 9:1111933.

PMID: 36726817 PMC: 9884710. DOI: 10.3389/fnut.2022.1111933.

References

Aigner E, Strasser M, Haufe H, Sonnweber T, Hohla F, Stadlmayr A . A role for low hepatic copper concentrations in nonalcoholic Fatty liver disease. Am J Gastroenterol. 2010; 105(9):1978-85. DOI: 10.1038/ajg.2010.170. View

Nobili V, Siotto M, Bedogni G, Rava L, Pietrobattista A, Panera N . Levels of serum ceruloplasmin associate with pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2012; 56(4):370-5. DOI: 10.1097/MPG.0b013e31827aced4. View

Pinhas-Hamiel O, Newfield R, Koren I, Agmon A, Lilos P, Phillip M . Greater prevalence of iron deficiency in overweight and obese children and adolescents. Int J Obes Relat Metab Disord. 2003; 27(3):416-8. DOI: 10.1038/sj.ijo.0802224. View

Ferrari M, Mistura L, Patterson E, Sjostrom M, Diaz L, Stehle P . Evaluation of iron status in European adolescents through biochemical iron indicators: the HELENA Study. Eur J Clin Nutr. 2011; 65(3):340-9. PMC: 3049292. DOI: 10.1038/ejcn.2010.279. View

Song M, Schuschke D, Zhou Z, Chen T, Pierce Jr W, Wang R . High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. J Hepatol. 2011; 56(2):433-40. PMC: 3261305. DOI: 10.1016/j.jhep.2011.05.030. View

Lima S, Arrais R, Sales C, Almeida M, de Sena K, Oliveira V . Assessment of copper and lipid profile in obese children and adolescents. Biol Trace Elem Res. 2007; 114(1-3):19-29. DOI: 10.1385/BTER:114:1:19. View

Wei Y, Rector R, Thyfault J, Ibdah J . Nonalcoholic fatty liver disease and mitochondrial dysfunction. World J Gastroenterol. 2008; 14(2):193-9. PMC: 2675113. DOI: 10.3748/wjg.14.193. View

Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J . Body iron metabolism and pathophysiology of iron overload. Int J Hematol. 2008; 88(1):7-15. PMC: 2516548. DOI: 10.1007/s12185-008-0120-5. View

Gehrke S, Kulaksiz H, Herrmann T, Riedel H, Bents K, Veltkamp C . Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron. Blood. 2003; 102(1):371-6. DOI: 10.1182/blood-2002-11-3610. View

10.

Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen B . IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004; 113(9):1271-6. PMC: 398432. DOI: 10.1172/JCI20945. View

11.

Tan T, Crawford D, Jaskowski L, Subramaniam V, Clouston A, Crane D . Excess iron modulates endoplasmic reticulum stress-associated pathways in a mouse model of alcohol and high-fat diet-induced liver injury. Lab Invest. 2013; 93(12):1295-312. DOI: 10.1038/labinvest.2013.121. View

12.

Laitinen R, Vuori E, Viikari J . Serum zinc and copper: associations with cholesterol and triglyceride levels in children and adolescents. Cardiovascular risk in young Finns. J Am Coll Nutr. 1989; 8(5):400-6. DOI: 10.1080/07315724.1989.10720314. View

13.

Ponka P, Beaumont C, Richardson D . Function and regulation of transferrin and ferritin. Semin Hematol. 1998; 35(1):35-54. View

14.

Al-Othman A, Rosenstein F, Lei K . Copper deficiency alters plasma pool size, percent composition and concentration of lipoprotein components in rats. J Nutr. 1992; 122(6):1199-204. DOI: 10.1093/jn/122.6.1199. View

15.

Aeberli I, Kaspar M, Zimmermann M . Dietary intake and physical activity of normal weight and overweight 6 to 14 year old Swiss children. Swiss Med Wkly. 2007; 137(29-30):424-30. DOI: 10.4414/smw.2007.11696. View

16.

Lee P, Beutler E . Regulation of hepcidin and iron-overload disease. Annu Rev Pathol. 2009; 4:489-515. DOI: 10.1146/annurev.pathol.4.110807.092205. View

17.

Halliwell B, Gutteridge J . Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. 1990; 186:1-85. DOI: 10.1016/0076-6879(90)86093-b. View

18.

Cayir Y, Cayir A, Turan M, Kurt N, Kara M, Laloglu E . Antioxidant status in blood of obese children: the relation between trace elements, paraoxonase, and arylesterase values. Biol Trace Elem Res. 2014; 160(2):155-60. DOI: 10.1007/s12011-014-0038-0. View

19.

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

20.

Mujica-Coopman M, Brito A, de Romana D, Pizarro F, Olivares M . Body mass index, iron absorption and iron status in childbearing age women. J Trace Elem Med Biol. 2014; 30:215-9. DOI: 10.1016/j.jtemb.2014.03.008. View