Body iron accumulation in obesity, diabetes and its complications, and the possibility of therapeutic application by iron regulation
Open accessAbstract
Iron is an essential trace metal element for maintaining vital functions, and it is involved in hemoglobin synthesis, redox reaction, enzyme activity, cell proliferation and apoptosis in various cells. Iron deficient-related diseases represented anemia are well-known, on the other hand, iron overload disease has attracted little attention. Excessive iron produces hydroxyl radicals via Fenton/Haber-Weiss reaction, causing organ damage in hereditary iron overload diseases. Additionally, it has been clarified that iron accumulation is involved in the pathological conditions even in metabolic diseases thought to be unrelated to iron so far. Therefore, the role of iron in the living body has been raised attention again. Recent studies have reported that body iron content is associated with both obesity and diabetes, and iron might be an aggravating factor of obesity and diabetes. We have revealed that iron chelating agent reduced oxidative stress and inflammation, suppressing the development of adipose hypertrophy in KKAy mice. Dietary iron restriction also diminishes oxidative stress, leading to the inhibition of increased albuminuria excretion and glomerular lesions in db/db mice. In this review, we give an outline of the role of iron on obese and diabetes, and diabetic kidney disease, and present the possibility of application to treatment with iron regulation in those disorders.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Iron deficiency is a common finding of metabolic alterations occurring in obesity.
“ID is a common finding of metabolic alterations occurring in obesity [11,67].”
From Iron Deficiency in Obesity and after Bariatric Surgery (2021) · cites this paper as [67]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Oxidative stress and diabetic complications
Giacco, F., & Brownlee, M. (2010) · Circulation Research · doi:10.1161/circresaha.110.223545 · Cited by 5,461 · see citing works
Andrews, N. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412607 · Cited by 2,130 · see citing works
Iron accumulation in Alzheimer disease is a source of redox-generated free radicals
Smith, M. A., Harris, P. L. R., Sayre, L. M., & Perry, G. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9866 · Cited by 1,357 · see citing works
Keaney, J. F., Larson, M. G., Vasan, R. S., Wilson, P. W. F., Lipinska, I., Corey, D., Massaro, J. M., Sutherland, P., Vita, J. A., & Benjamin, E. J. (2003) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000058402.34138.11 · Cited by 1,304 · see citing works
Pou, K. M., Massaro, J. M., Hoffmann, U., Vasan, R. S., Maurovich‐Horvat, P., Larson, M. G., Keaney, J. F., Meigs, J. B., Lipinska, I., Kathiresan, S., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.710509 · Cited by 898 · see citing works
R�sen, P., Nawroth, P., King, G. L., M�ller, W., Tritschler, H., & Packer, L. (2001) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.196 · Cited by 881 · see citing works
Kakhlon, O., & Cabantchik, Z. I. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)01006-7 · Cited by 839 · see citing works
Cross-Talk Between Iron Metabolism and Diabetes
Fernández-Real, J. M., López-Bermejo, A., & Ricart, W. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2348 · Cited by 704 · see citing works
Labile iron pool: the main determinant of cellular response to oxidative stress
Kruszewski, M. K. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.004 · Cited by 529 · see citing works
Reactive Oxygen Species-Regulated Signaling Pathways in Diabetic Nephropathy
Lee, H. B., Yu, M.-R., Yang, Y., Jiang, Z., & Ha, H. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000077410.66390.0f · Cited by 468 · see citing works
The Role of Iron in Diabetes and Its Complications
Swaminathan, S., Fonseca, V. A., Alam, M. G., & Shah, S. V. (2007) · Diabetes Care · doi:10.2337/dc06-2625 · Cited by 423 · see citing works
Diabetes and serum ferritin concentration among U.S. adults.
Ford, E. S., & Cogswell, M. E. (1999) · Diabetes Care · doi:10.2337/diacare.22.12.1978 · Cited by 419 · see citing works
Blood Letting in High-Ferritin Type 2 Diabetes
Fernández‐Real, J. M., Peñarroja, G., Castro, A., Garcia-Bragado, F., Hernández‐Aguado, I., & Ricart, W. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1000 · Cited by 333 · see citing works
Redox signaling and cancer: The role of “labile” iron
Galaris, D., Skiada, V., & Barbouti, A. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.02.038 · Cited by 284 · see citing works
Lewis, G. F. (2002) · Endocrine Reviews · doi:10.1210/er.23.2.201 · Cited by 281 · see citing works
Iron Promotes the Toxicity of Amyloid β Peptide by Impeding Its Ordered Aggregation
Liu, B., Moloney, A. M., Meehan, S., Morris, K. L., Thomas, S. E., Serpell, L. C., Hider, R. C., Marciniak, S. J., Lomas, D. A., & Crowther, D. C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.158980 · Cited by 217 · see citing works
Metal Chelation as a Potential Therapy for Alzheimer's Disease
Cuajungco, M. P., Faget, K. Y., Huang, X., Tanzi, R. E., & Bush, A. I. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06938.x · Cited by 215 · see citing works
Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders
Camaschella, C. (2005) · Blood · doi:10.1182/blood-2005-05-1857 · Cited by 194 · see citing works
Cairo, G., Recalcati, S., Pietrangelo, A., & Minotti, G. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00825-0 · Cited by 176 · see citing works
Obesity Alters Adipose Tissue Macrophage Iron Content and Tissue Iron Distribution
Orr, J. S., Kennedy, A. J., Anderson‐Baucum, E. K., Webb, C. D., Fordahl, S. C., Erikson, K. M., Zhang, Y., Etzerodt, A., Moestrup, S. K., & Hasty, A. H. (2013) · Diabetes · doi:10.2337/db13-0213 · Cited by 172 · see citing works
Serum Ferritin Is Associated With Visceral Fat Area and Subcutaneous Fat Area
Iwasaki, T., Nakajima, A., Yoneda, M., Yamada, Y., Mukasa, K., Fujita, K., Fujisawa, N., Wada, K., & Terauchi, Y. (2005) · Diabetes Care · doi:10.2337/diacare.28.10.2486 · Cited by 171 · see citing works
Cooksey, R. C., Jones, D., Gabrielsen, S., Huang, J., Simcox, J., Luo, B., Soesanto, Y., Rienhoff, H. Y., Abel, E. D., & McClain, D. A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00022.2010 · Cited by 168 · see citing works
Common Presence of Non–Transferrin-Bound Iron Among Patients With Type 2 Diabetes
Lee, D.-H., Liu, D. Y., Jacobs, D. R., Shin, H.-R., Song, K., Lee, I.-K., Kim, B., & Hider, R. C. (2006) · Diabetes Care · doi:10.2337/dc05-2471 · Cited by 128 · see citing works
Deferoxamine Therapy in High-Ferritin Diabetes
Cutler, P. (1989) · Diabetes · doi:10.2337/diab.38.10.1207 · Cited by 111 · see citing works
Iron restriction improves type 2 diabetes mellitus in Otsuka Long-Evans Tokushima fatty rats
Minamiyama, Y., Takemura, S., Kodai, S., Shinkawa, H., Tsukioka, T., Ichikawa, H., Naito, Y., Yoshikawa, T., & Okada, S. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00620.2009 · Cited by 89 · see citing works
Biomarkers of body iron stores and risk of developing type 2 diabetes
Rajpathak, S. N., Wylie‐Rosett, J., Gunter, M. J., Negassa, A., Kabat, G. C., Rohan, T. E., & Crandall, J. P. (2009) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2008.00985.x · Cited by 85 · see citing works
Hayashi, H., Takikawa, T., Nishimura, N., & Yano, M. (1995) · Journal of Hepatology · doi:10.1016/0168-8278(95)80278-9 · Cited by 59 · see citing works
Dietary iron restriction inhibits progression of diabetic nephropathy indb/dbmice
Ikeda, Y., Enomoto, H., Tajima, S., Izawa‐Ishizawa, Y., Kihira, Y., Ishizawa, K., Tomita, S., Tsuchiya, K., & Tamaki, T. (2013) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00473.2012 · Cited by 53 · see citing works
Self-citationRegulation of LIP Level and ROS Formation Through Interaction of H-Ferritin with G-CSF Receptor
Yuan, X., Cong, Y., Hao, J., Shan, Y., Zhao, Z., Wang, S., & Chen, J. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.03.027 · Cited by 49 · see citing works
Ikeda, Y., Satoh, A., Horinouchi, Y., Hamano, H., Watanabe, H., Imao, M., Imanishi, M., Zamami, Y., Takechi, K., Izawa‐Ishizawa, Y., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201802724rr · Cited by 49 · see citing works
Self-citationInteroceptive and integrative contributions of forebrain and brainstem to energy balance control
Grill, H. J., & Kaplan, J. M. (2001) · International Journal of Obesity · doi:10.1038/sj/ijo/0801917 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 33
- Cairo G, et al. Free Radic Biol Med. 2002;32:1237-1243.
- Kakhlon O, et al. Free Radic Biol Med. 2002;33:1037-1046.
- Kruszewski M. Mutat Res. 2003;531:81-92.
- Yuan X, et al. J Mol Biol. 2004;339:131-144.
- Andrews NC. N Engl J Med. 1999;341:1986-1995.
- Camaschella C. Blood. 2005;106:3710-3717.
- Hayashi H, et al. Am J Gastroenterol. 1994;89:986-988.
- Hayashi H, et al. J Hepatol. 1995;22:268-271.
- Cuajungco MP, et al. Ann N Y Acad Sci. 2000;920:292-304.
- Smith MA, et al. Proc Natl Acad Sci U S A. 1997;94:9866-9868.
- Liu B, et al. J Biol Chem. 2011;286:4248-4256.
- Shoham S, et al. Cell Mol Biol (Noisy-le-grand). 2000;46:743-760.
- Galaris D, et al. Cancer Lett. 2008;266:21-29.
- Lewis GF, et al. Endocr Rev. 2002;23:201-229.
- Gillum RF. Int J Obes Relat Metab Disord. 2001;25:639-645.
- Iwasaki T, et al. Diabetes Care. 2005;28:2486-2491.
- Rajpathak SN, et al. Diabetes Obes Metab. 2009;11:472-479.
- Lee DH, et al. Diabetes Care. 2006;29:1090-1095.
- Ford ES, et al. Diabetes Care. 1999;22:1978-1983.
- Rösen P, et al. Diabetes Metab Res Rev. 2001;17:189-212.
- Giacco F, et al. Circ Res. 2010;107:1058-1070.
- Keaney JF, et al. Arterioscler Thromb Vasc Biol. 2003;23:434-439.
- Pou KM, et al. Circulation. 2007;116:1234-1241.
- Fernández-Real JM, et al. Diabetes. 2002;51:2348-2354.
- Swaminathan S, et al. Diabetes Care. 2007;30:1926-1933.
- Orr, J.S., et al. Diabetes 2014;63:421-432.
- Tajima S, et al. Am J Physiol Endocrinol Metab. 2012;302: E77-E86.
- Ikeda Y, et al. Am J Physiol Renal Physiol. 2013;304:F1028- F1036.
- Minamiyama Y, et al. Am J Physiol Endocrinol Metab. 2010;298: E1140-E1149.
- Cooksey RC, et al. Am J Physiol Endocrinol Metab. 2010;298: E1236-E1243.
- Cutler P. Diabetes. 1989;38:1207-1210.
- Fernández-Real JM, et al. Diabetes. 2002;51:1000-1004.
- Ikeda Y, et al. FASEB J. 2019;33:9551-9564. 図 6 肥満・糖尿病,糖尿病性臓器合併症への鉄の関与
Cited by
Sorted by citations
Iron Deficiency in Obesity and after Bariatric Surgery
Bjørklund, G., Peana, M., Pivina, L., Dosa, A., Aaseth, J., Semenova, Y., Chirumbolo, S., Medici, S., Dadar, M., & Costea, D.-O. (2021) · Biomolecules · doi:10.3390/biom11050613 · Cited by 99 · see citing works
- Authors
- Horinouchi, Y., Ikeda, Y., & Tamaki, T.
- Affiliations
- Tokushima University (JP)
- ORCID
- Ikeda, Yasumasa
- Venue
- Folia Pharmacologica Japonica
- Publisher
- Japanese Pharmacological Society
- Published
- 2019
- Volume
- 154
- Issue
- 6
- Pages
- 316-321
- ISSN
- 0015-5691 (ISSN-L)
- 1347-8397
- OpenAlex
- W2993920348
- Cited by
- 8
- References
- 31
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 2 · 2021: 1
- FWCI
- 0.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Folia Pharmacologica Japonica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (18K08480, 18K14983)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- obesity, diabetes mellitus, diabetic nephropathy, iron chelation, dietary iron restriction, oxidative stress, inflammation, albuminuria, glomerular lesions, iron overload, KK-Ay mice, db/db mice
- MeSH terms
- Animals, Diabetes Mellitus, Diabetic Nephropathies, Humans, Iron, Obesity, Oxidative Stress, Iron, Dietary, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review