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Effects of the iron transporter inhibitor ferristatin II on serum iron and lipid metabolism
Author(s) -
Kim Jonghan,
Buckett Peter,
WesslingResnick Marianne
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.223.7
Subject(s) - serum iron , hepcidin , transferrin saturation , hypertriglyceridemia , medicine , endocrinology , metabolism , lipid metabolism , chemistry , transferrin , triglyceride , anemia , iron deficiency , cholesterol
Iron loading is associated with altered lipid metabolism, but underlying mechanisms and clinical consequences remain unknown. We have shown that Belgrade rats, a genetic model of iron‐loading anemia, have elevated serum triglyceride (TG). To explore whether lowering serum iron would influence serum TG, we characterized effects of the small molecule iron transport inhibitor ferristatin II (NSC8679). Rats injected with up to 40 mg ferristatin II/kg twice daily for up to 4 days had lower serum iron and transferrin saturation. Urinary analysis confirmed drug metabolism by acetylation. Rats treated with ferristatin II had lower intestinal uptake of 59Fe, associated with up‐regulation of the iron regulatory hormone hepcidin. Treatment with ferristatin II decreased serum iron in Belgrade rats, and serum TG was significantly reduced. Our study provides an explanation for the relationship between iron loading and lipid metabolism, as well as mechanistic support for interventions that reduce serum iron levels in individuals at risk for hypertriglyceridemia. Supported by NIH DK086774, DK064750 and ES014638.