title: Iron loading impairs lipoprotein lipase activity and promotes hypertriglyceridemia.
abstract: Iron loading is associated with altered lipid metabolism, but underlying mechanisms remain unknown. We compared serum iron and triglycerides (TGs) in Belgrade rats, a genetic model of iron-loading anemia. Homozygous b/b rats had greater serum iron (68 vs. 28 μM; P=0.0004) and TG levels (180 vs. 84 mg/dl; P=0.014) compared to +/b controls. To confirm the association between iron loading and high TGs, Fischer rats were fed chow containing 1% carbonyl iron. Compared to controls pair-fed normal chow, carbonyl iron-fed rats had elevated serum iron (42 vs. 21 μM; P=0.007) and TGs (190 vs. 115 mg/dl; P=0.009). Despite normal hepatic production and secretion, TG clearance was lower in b/b than +/b rats due to reduced serum lipoprotein lipase (LPL) activity (3.1 vs. 5.0 mM/min; P=0.026). Likewise, LPL was lower in carbonyl iron-fed rats compared to controls (2.4 vs. 3.7 mM/min; P=0.017). Direct addition of iron to serum ex vivo or recombinant LPL in vitro decreased enzymatic activity in a dose-dependent manner. Lowering serum iron in Belgrade rats reduced TG levels (274 to 67 mg/dl, P=0.001). This study explains the relationship between iron status and lipid metabolism and provides mechanistic support for interventions that reduce serum iron levels in individuals at risk for hypertriglyceridemia.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Jonghan
authors.initials: J
authors.lastname: Kim
authors.forename: Xuming
authors.initials: X
authors.lastname: Jia
authors.forename: Peter D
authors.initials: PD
authors.lastname: Buckett
authors.forename: Sihao
authors.initials: S
authors.lastname: Liu
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lee
authors.forename: Marianne
authors.initials: M
authors.lastname: Wessling-Resnick
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015228:Hypertriglyceridemia / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000097:blood*; D000090463:Iron Deficiencies; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides; D007501:Iron; D008071:Lipoprotein Lipase