Obesity as an emerging risk factor for iron deficiency

Nutrients

Volumn 6, Issue 9, 2014, Pages 3587-3600

  Aigner, Elmar ^a   Feldman, Alexandra ^a   Datz, Christian ^a,b  

^a PARACELSUS MEDICAL UNIVERSITY   (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Hepcidin; Insulin resistance; Iron deficiency; Obesity

Indexed keywords

ADIPOCYTOKINE; ERYTHROPOIETIN; FATTY ACID BINDING PROTEIN 4; FERRIC ION; FERROPORTIN; FERROUS ION; HEMOGLOBIN; HEPCIDIN; HEPHAESTIN; INTERLEUKIN 1; INTERLEUKIN 6; IRON; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; TRANSFERRIN RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

ADIPOSE TISSUE; BARIATRIC SURGERY; BILIOPANCREATIC BYPASS; BODY MASS; HOMEOSTASIS AND REGULATION; HUMAN; INFLAMMATION; INSULIN RESISTANCE; IRON ABSORPTION; IRON DEFICIENCY; IRON METABOLISM; IRON OVERLOAD; IRON TRANSPORT; METABOLIC SYNDROME X; NONALCOHOLIC FATTY LIVER; OBESITY; PATHOPHYSIOLOGY; PHENOTYPE; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; ROUX Y ANASTOMOSIS; SUPPLEMENTATION; WEIGHT REDUCTION; ANEMIA, IRON-DEFICIENCY; COMPLICATION; DEFICIENCY; INTESTINE ABSORPTION; METABOLISM; NUTRITIONAL STATUS;

ANEMIA, IRON-DEFICIENCY; BARIATRIC SURGERY; HUMANS; INTESTINAL ABSORPTION; IRON; NUTRITIONAL STATUS; OBESITY;

EID: 84907214696     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu6093587     Document Type: Review

References (80)

1. Low, S.; Chin, M.C.; Deurenberg-Yap, M. Review on epidemic of obesity. Ann. Acad. Med.Singapore 2009, 38, 57–59.
2. Datz, C.; Felder, T.K.; Niederseer, D.; Aigner, E. Iron homeostasis in the metabolic syndrome. Eur.J. Clin. Investig. 2013, 43, 215–224.
3. Lear, S.A.; Teo, K.; Gasevic, D.; Zhang, X.; Poirier, P.P.; Rangarajan, S.; Seron, P.; Kelishadi, R.; Tamil, A.M.; Kruger, A. et al. The association between ownership of common household devices and obesity and diabetes in high, middle and low income countries. Can. Med. Assoc. J. 2014, 186, 258–266.
4. Myint, P.K.; Kwok, C.S.; Luben, R.N.; Wareham, N.J.; Khaw, K.T. Body fat percentage, body mass index and waist-to-hip ratio as predictors of mortality and cardiovascular disease. Heart 2014, doi:10.1136/heartjnl-2014-305816.
5. Noto, H.; Goto, A.; Tsujimoto, T.; Osame, K.; Noda, M. Latest insights into the risk of cancer in diabetes. J. Diabetes Investig. 2013, 4, 225–232.
6. Dongiovanni, P.; Fracanzani, A.L.; Fargion, S.; Valenti, L. Iron in fatty liver and in the metabolic syndrome: A promising therapeutic target. J. Hepatol. 2011, 55, 920–932.
7. Weisberg, S.P.; McCann, D.; Desai, M.; Rosenbaum, M.; Leibel, R.L.; Ferrante, A.W. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Investig. 2003, 112, 1796–1808.
8. Tilg, H.; Moschen, A.R. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat. Rev. 2006, 6, 772–783.
9. Mather, K.J.; Goldberg, R.B. Clinical use of adiponectin as a marker of metabolic dysregulation. Best Pract. Res. Clin. Endocrinol. Metab. 2014, 28, 107–117.
10. DePaoli, A. Leptin in common obesity and associated disorders of metabolism. J. Endocrinol. 2014, doi:10.1530/JOE-14-0258.
11. Flehmig, G.; Scholz, M.; Kloting, N.; Fasshauer, M.; Tonjes, A.; Stumvoll, M.; Youn, B.S.; Bluher, M. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation. PLoS One 2014, 9, e99785.
12. Wu, L.E.; Samocha-Bonet, D.; Whitworth, P.T.; Fazakerley, D.J.; Turner, N.; Biden, T.J.; James, D.E.; Cantley, J. Identification of fatty acid binding protein 4 as an adipokine that regulates insulin secretion during obesity. Mol. Metab. 2014, 3, 465–473.
13. Cusi, K. The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes. Curr.Diabetes Rep. 2010, 10, 306–315.
14. Schwenger, K.J.; Allard, J.P. Clinical approaches to non-alcoholic fatty liver disease. World J.Gastroenterol. 2014, 20, 1712–1723.
15. Hentze, M.W.; Muckenthaler, M.U.; Galy, B.; Camaschella, C. Two to tango: Regulation of mammalian iron metabolism. Cell 2010, 142, 24–38.
16. Gunshin, H.; Mackenzie, B.; Berger, U.V.; Gunshin, Y.; Romero, M.F.; Boron, W.F.; Nussberger, S.; Gollan, J.L.; Hediger, M.A. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997, 388, 482–488.
17. Abboud, S.; Haile, D.J. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 2000, 275, 19906–19912.
18. Vulpe, C.D.; Kuo, Y.M.; Murphy, T.L.; Cowley, L.; Askwith, C.; Libina, N.; Gitschier, J.; Anderson, G.J. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat. Genet. 1999, 21, 195–199.
19. Korolnek, T.; Hamza, I. Like iron in the blood of the people: The requirement for heme trafficking in iron metabolism. Front Pharmacol. 2014, 5, 126.
20. Ganz, T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003, 102, 783–788.
21. Nemeth, E.; Tuttle, M.S.; Powelson, J.; Vaughn, M.B.; Donovan, A.; Ward, D.M.; Ganz, T.; Kaplan, J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004, 306, 2090–2093.
22. Bekri, S.; Gual, P.; Anty, R.; Luciani, N.; Dahman, M.; Ramesh, B.; Iannelli, A.; Staccini-Myx, A.; Casanova, D.; Ben Amor, I. et al. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and nash. Gastroenterology 2006, 131, 788–796.
23. Kulaksiz, H.; Fein, E.; Redecker, P.; Stremmel, W.; Adler, G.; Cetin, Y. Pancreatic beta-cells express hepcidin, an iron-uptake regulatory peptide. J. Endocrinol. 2008, 197, 241–249.
24. Wenzel, B.J.; Stults, H.B.; Mayer, J. Hypoferraemia in obese adolescents. Lancet 1962, 2, 327–328.
25. Seltzer, C.C.; Mayer, J. Serum iron and iron-binding capacity in adolescents. Ii.Comparison of obese and nonobese subjects. Am. J. Clin. Nutr. 1963, 13, 354–361.
26. Manios, Y.; Moschonis, G.; Chrousos, G.P.; Lionis, C.; Mougios, V.; Kantilafti, M.; Tzotzola, V.; Skenderi, K.P.; Petridou, A.; Tsalis, G. et al. The double burden of obesity and iron deficiency on children and adolescents in greece: The healthy growth study. J. Hum. Nutr. Diet. 2013, 26, 470–478.
27. Nead, K.G.; Halterman, J.S.; Kaczorowski, J.M.; Auinger, P.; Weitzman, M. Overweight children and adolescents: A risk group for iron deficiency. Pediatrics 2004, 114, 104–108.
28. Pinhas-Hamiel, O.; Newfield, R.S.; 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, 416–418.
29. Moayeri, H.; Bidad, K.; Zadhoush, S.; Gholami, N.; Anari, S. Increasing prevalence of iron deficiency in overweight and obese children and adolescents (tehran adolescent obesity study). Eur.J. Pediatr. 2006, 165, 813–814.
30. Shi, Z.; Lien, N.; Kumar, B.N.; Dalen, I.; Holmboe-Ottesen, G. The sociodemographic correlates of nutritional status of school adolescents in jiangsu province, china. J. Adolesc. Health 2005, 37, 313–322.
31. Tussing-Humphreys, L.M.; Liang, H.; Nemeth, E.; Freels, S.; Braunschweig, C.A. Excess adiposity, inflammation, and iron-deficiency in female adolescents. J. Am. Diet. Assoc. 2009, 109, 297–302.
32. Sanad, M.; Osman, M.; Gharib, A. Obesity modulate serum hepcidin and treatment outcome of iron deficiency anemia in children: A case control study. Ital. J. Pediatr. 2011, 37, 34.
33. Aigner, E.; Hinz, C.; Steiner, K.; Rossmann, B.; Pfleger, J.; Hohla, F.; Steger, B.; Stadlmayr, A.; Patsch, W.; Datz, C. Iron stores, liver transaminase levels and metabolic risk in healthy teenagers. Eur. J. Clin. Investig. 2010, 40, 155–163.
34. Micozzi, M.S.; Albanes, D.; Stevens, R.G. Relation of body size and composition to clinical biochemical and hematologic indices in us men and women. Am. J. Clin. Nutr. 1989, 50, 1276–1281.
35. Ozata, M.; Mergen, M.; Oktenli, C.; Aydin, A.; Sanisoglu, S.Y.; Bolu, E.; Yilmaz, M.I.; Sayal, A.; Isimer, A.; Ozdemir, I.C. Increased oxidative stress and hypozincemia in male obesity. Clin.Biochem. 2002, 35, 627–631.
36. Lefebvre, P.; Letois, F.; Sultan, A.; Nocca, D.; Mura, T.; Galtier, F. Nutrient deficiencies in patients with obesity considering bariatric surgery: A cross-sectional study. Surg. Obes. Relat. Dis. 2014, 10, 540–546.
37. Cheng, H.L.; Bryant, C.; Cook, R.; O’Connor, H.; Rooney, K.; Steinbeck, K. The relationship between obesity and hypoferraemia in adults: A systematic review. Obes. Rev. 2012, 13, 150–161.
38. Cepeda-Lopez, A.C.; Osendarp, S.J.; Melse-Boonstra, A.; Aeberli, I.; Gonzalez-Salazar, F.; Feskens, E.; Villalpando, S.; Zimmermann, M.B. Sharply higher rates of iron deficiency in obese mexican women and children are predicted by obesity-related inflammation rather than by differences in dietary iron intake. Am. J. Clin. Nutr. 2011, 93, 975–983.
39. Tussing-Humphreys, L.M.; Nemeth, E.; Fantuzzi, G.; Freels, S.; Guzman, G.; Holterman, A.X.; Braunschweig, C. Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity (Silver Spring) 2010, 18, 1449–1456.
40. Gong, L.; Yuan, F.; Teng, J.; Li, X.; Zheng, S.; Lin, L.; Deng, H.; Ma, G.; Sun, C.; Li, Y. Weight loss, inflammatory markers, and improvements of iron status in overweight and obese children. J. Pediatr. 2014, 164, 795–800.e2.
41. Amato, A.; Santoro, N.; Calabro, P.; Grandone, A.; Swinkels, D.W.; Perrone, L.; del Giudice, E.M. Effect of body mass index reduction on serum hepcidin levels and iron status in obese children. Int.J. Obes. 2010, 34, 1772–1774.
42. Di Toro, A.; Marotta, A.; Todisco, N.; Ponticiello, E.; Collini, R.; Di Lascio, R.; Perrone, L. Unchanged iron and copper and increased zinc in the blood of obese children after two hypocaloric diets. Biol. Trace Elem. Res. 1997, 57, 97–104.
43. Beard, J.; Borel, M.; Peterson, F.J. Changes in iron status during weight loss with very-low-energy diets. Am. J. Clin. Nutr. 1997, 66, 104–110.
44. Tussing-Humphreys, L.M.; Nemeth, E.; Fantuzzi, G.; Freels, S.; Holterman, A.X.; Galvani, C.; Ayloo, S.; Vitello, J.; Braunschweig, C. Decreased serum hepcidin and improved functional iron status 6 months after restrictive bariatric surgery. Obesity (Silver Spring) 2010, 18, 2010–2016.
45. Munoz, M.; Botella-Romero, F.; Gomez-Ramirez, S.; Campos, A.; Garcia-Erce, J.A. Iron deficiency and anaemia in bariatric surgical patients: Causes, diagnosis and proper management. Nutr. Hosp. 2009, 24, 640–654.
46. Aktas, G.; Alcelik, A.; Yalcin, A.; Karacay, S.; Kurt, S.; Akduman, M.; Savli, H. Treatment of iron deficiency anemia induces weight loss and improves metabolic parameters. Clin. Ter. 2014, 165, e87–e89.
47. Fried, M.; Yumuk, V.; Oppert, J.M.; Scopinaro, N.; Torres, A.; Weiner, R.; Yashkov, Y.; Fruhbeck, G. Interdisciplinary european guidelines on metabolic and bariatric surgery. Obes. Surg. 2014, 24, 42–55.
48. Baptista, V.; Wassef, W. Bariatric procedures: An update on techniques, outcomes and complications. Curr. Opin. Gastroenterol. 2013, 29, 684–693.
49. Patel, S.R.; Hakim, D.; Mason, J.; Hakim, N. The duodenal-jejunal bypasssleeve (endobarrier gastrointestinal liner) for weight loss and treatment of type 2 diabetes. Surg. Obes. Relat. Dis. 2013, 9, 482–484.
50. Flancbaum, L.; Belsley, S.; Drake, V.; Colarusso, T.; Tayler, E. Preoperative nutritional status of patients undergoing roux-en-y gastric bypass for morbid obesity. J. Gastrointest. Surg. 2006, 10,1033–1037.
51. Damms-Machado, A.; Friedrich, A.; Kramer, K.M.; Stingel, K.; Meile, T.; Kuper, M.A.; Konigsrainer, A.; Bischoff, S.C. Pre- and postoperative nutritional deficiencies in obese patients undergoing laparoscopic sleeve gastrectomy. Obes. Surg. 2012, 22, 881–889.
52. Ernst, B.; Thurnheer, M.; Schmid, S.M.; Schultes, B. Evidence for the necessity to systematically assess micronutrient status prior to bariatric surgery. Obes. Surg. 2009, 19, 66–73.
53. Harju, E. Empty iron stores as a significant risk factor in abdominal surgery. J. Parenter. Enteral Nutr. 1988, 12, 282–285.
54. Hallet, J.; Hanif, A.; Callum, J.; Pronina, I.; Wallace, D.; Yohanathan, L.; McLeod, R.; Coburn, N. The impact of perioperative iron on the use of red blood cell transfusions in gastrointestinal surgery: A systematic review and meta-analysis. Transfus. Med. Rev. 2014, doi: 10.1016/ j.tmrv.2014.05.004.
55. Shander, A.; Van Aken, H.; Colomina, M.J.; Gombotz, H.; Hofmann, A.; Krauspe, R.; Lasocki, S.; Richards, T.; Slappendel, R.; Spahn, D.R. Patient blood management in europe. Br. J. Anaesth. 2012, 109, 55–68.
56. 2). Obes. Surg. 2014, 24, 197–204.
57. Coupaye, M.; Puchaux, K.; Bogard, C.; Msika, S.; Jouet, P.; Clerici, C.; Larger, E.; Ledoux, S. Nutritional consequences of adjustable gastric banding and gastric bypass: A 1-year prospective study. Obes. Surg. 2009, 19, 56–65.
58. Alexandrou, A.; Armeni, E.; Kouskouni, E.; Tsoka, E.; Diamantis, T.; Lambrinoudaki, I. Cross-sectional long-term micronutrient deficiencies after sleeve gastrectomy versus roux-en-y gastric bypass: A pilot study. Surg. Obes. Relat. Dis. 2014, 10, 262–268.
59. Gehrer, S.; Kern, B.; Peters, T.; Christoffel-Courtin, C.; Peterli, R. Fewer nutrient deficiencies after laparoscopic sleeve gastrectomy (lsg) than after laparoscopic roux-y-gastric bypass (lrygb)-aprospective study. Obes. Surg. 2010, 20, 447–453.
60. Anty, R.; Dahman, M.; Iannelli, A.; Gual, P.; Staccini-Myx, A.; Amor, I.B.; Luciani, N.; Saint-Paul, M.C.; Huet, P.M.; Sadoul, J.L. et al. Bariatric surgery can correct iron depletion in morbidly obese women: A link with chronic inflammation. Obes. Surg. 2008, 18, 709–714.
61. Ramalho, R.; Guimaraes, C.; Gil, C.; Neves, C.; Guimaraes, J.T.; Delgado, L. Morbid obesity and inflammation: A prospective study after adjustable gastric banding surgery. Obes. Surg. 2009, 19, 915–920.
62. Mechanick, J.I.; Youdim, A.; Jones, D.B.; Garvey, W.T.; Hurley, D.L.; McMahon, M.M.; Heinberg, L.J.; Kushner, R.; Adams, T.D.; Shikora, S. et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient—2013 update: Cosponsored by american association of clinical endocrinologists, the obesity society, and american society for metabolic & bariatric surgery. Obesity (Silver Spring) 2013, 21 (Suppl. 1),S1–S27.
63. Gesquiere, I.; Lannoo, M.; Augustijns, P.; Matthys, C.; Van der Schueren, B.; Foulon, V. Iron deficiency after roux-en-y gastric bypass: Insufficient iron absorption from oral iron supplements. Obes. Surg. 2014, 24, 56–61.
64. Marambio, A.; Watkins, G.; Castro, F.; Riffo, A.; Zuniga, R.; Jans, J.; Villanueva, M.E.; Diaz, G. Changes in iron transporter divalent metal transporter 1 in proximal jejunum after gastric bypass. World J. Gastroenterol. 2014, 20, 6534–6540.
65. Ruz, M.; Carrasco, F.; Rojas, P.; Codoceo, J.; Inostroza, J.; Basfi-Fer, K.; Valencia, A.; Csendes, A.; Papapietro, K.; Pizarro, F. et al. Heme- and nonheme-iron absorption and iron status 12 mo after sleeve gastrectomy and roux-en-y gastric bypass in morbidly obese women. Am. J. Clin. Nutr. 2012, 96, 810–817.
66. Santos, J.; Salgado, P.; Santos, C.; Mendes, P.; Saavedra, J.; Baldaque, P.; Monteiro, L.; Costa, E. Effect of bariatric surgery on weight loss, inflammation, iron metabolism, and lipid profile. Scand.J. Surg. 2014, 103, 21–25.
67. Mujica-Coopman, M.F.; Brito, A.; Lopez 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, doi:10.1016/j.jtemb.2014.03.008.
68. Zimmermann, M.B.; Zeder, C.; Muthayya, S.; Winichagoon, P.; Chaouki, N.; Aeberli, I.; Hurrell, R.F. Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification. Int. J. Obes. 2008, 32, 1098–1104.
69. del Giudice, E.M.; Santoro, N.; Amato, A.; Brienza, C.; Calabro, P.; Wiegerinck, E.T.; Cirillo, G.; Tartaglione, N.; Grandone, A.; Swinkels, D.W. et al. Hepcidin in obese children as a potential mediator of the association between obesity and iron deficiency. J. Clin. Endocrinol. Metab. 2009, 94, 5102–5107.
70. Aeberli, I.; Hurrell, R.F.; Zimmermann, M.B. Overweight children have higher circulating hepcidin concentrations and lower iron status but have dietary iron intakes and bioavailability comparable with normal weight children. Int. J. Obes. 2009, 33, 1111–1117.
71. Aigner, E.; Theurl, I.; Theurl, M.; Lederer, D.; Haufe, H.; Dietze, O.; Strasser, M.; Datz, C.; Weiss, G. Pathways underlying iron accumulation in human nonalcoholic fatty liver disease. Am. J. Clin.Nutr. 2008, 87, 1374–1383.
72. Barisani, D.; Pelucchi, S.; Mariani, R.; Galimberti, S.; Trombini, P.; Fumagalli, D.; Meneveri, R.; Nemeth, E.; Ganz, T.; Piperno, A. Hepcidin and iron-related gene expression in subjects with dysmetabolic hepatic iron overload. J. Hepatol. 2008, 49, 123–133.
73. Ruivard, M.; Laine, F.; Ganz, T.; Olbina, G.; Westerman, M.; Nemeth, E.; Rambeau, M.; Mazur, A.; Gerbaud, L.; Tournilhac, V. et al. Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin. J. Hepatol. 2009, 50, 1219–1225.
74. McClung, J.P.; Karl, J.P. Iron deficiency and obesity: The contribution of inflammation and diminished iron absorption. Nutr. Rev. 2009, 67, 100–104.
75. Tussing-Humphreys, L.; Frayn, K.N.; Smith, S.R.; Westerman, M.; Dennis, A.L.; Nemeth, E.; Thomson, J.; Pusatcioglu, C. Subcutaneous adipose tissue from obese and lean adults does not release hepcidin in vivo. Sci. World J. 2011, 11, 2197–2206.
76. Ganz, T.; Nemeth, E. Iron sequestration and anemia of inflammation. Semin. Hematol. 2009, 46, 387–393.
77. Nairz, M.; Haschka, D.; Demetz, E.; Weiss, G. Iron at the interface of immunity and infection. Front Pharmacol. 2014, 5, 152.
78. Sonnweber, T.; Ress, C.; Nairz, M.; Theurl, I.; Schroll, A.; Murphy, A.T.; Wroblewski, V.; Witcher, D.R.; Moser, P.; Ebenbichler, C.F. et al. High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption. J. Nutr. Biochem. 2012, 23, 1600–1608.
79. Aigner, E.; Theurl, I.; Haufe, H.; Seifert, M.; Hohla, F.; Scharinger, L.; Stickel, F.; Mourlane, F.; Weiss, G.; Datz, C. Copper availability contributes to iron perturbations in human nonalcoholic fatty liver disease. Gastroenterology 2008, 135, 680–688.
80. Matak, P.; Zumerle, S.; Mastrogiannaki, M.; El Balkhi, S.; Delga, S.; Mathieu, J.R.; Canonne-Hergaux, F.; Poupon, J.; Sharp, P.A.; Vaulont, S. et al. Copper deficiency leads to anemia, duodenal hypoxia, upregulation of hif-2alpha and altered expression of iron absorption genes in mice. PLoS One 2013, 8, e59538.