Effect of iron status on lipid and glucose metabolism

Belgrade ( b/b ) rats have impaired divalent metal transporter‐1 (DMT1) activity and display iron‐loading anemia. To investigate the relationship between iron status and lipid/glucose metabolism, we characterized the metabolic phenotype of b/b rats. Fasting serum triglyceride (TG) levels were higher in homozygous b/b rats compared to heterozygous littermate ( +/b ) control rats at the age of 6–18 weeks. By 18 weeks of age, b/b rats also exhibited mild hyperglycemia. Although serum insulin level was reduced in b/b rats, its secretion was not affected; rather, b/b rats were insulin‐sensitive, suggesting that b/b rats have altered lipid metabolism and consequently, impaired glucose homeostasis. These alterations appear to be related to iron‐loading since anemic +/b rats fed an iron deficient diet showed normal serum TG. Neither hepatic TG levels nor lipogenic gene expression was altered in b/b rats. After injection with Triton WR1339, a lipoprotein lipase inhibitor, TG secretion kinetics were unchanged in b/b rats, suggesting that hypertriglyceridemia results from reduced TG clearance and not from enhanced TG secretion. The apoE/apoB lipoprotein ratio in b/b rats was 50% of that observed for +/b rats, further supporting the idea that b/b rats have slower plasma VLDL removal. Supported by NIH R90 DK071507 and R01 ES014638. Grant Funding Source : NIH