Diet-induced obesity leads to decreased hepatic iron storage in mice

Abstract

An increased risk of iron deficiency has been reported in obese individuals. We investigated hepatic iron status and serum levels of both adipokines and inflammatory markers in obese mice to test the hypothesis that high-fat-diet (HFD)-induced obesity leads to reduced iron storage associated with inflammation. Four-week-old C57BL mice were fed a HFD containing 60% energy from fat for 16 weeks and were compared with mice on a control diet with 10% energy from fat. The HFD group had significantly higher levels of leptin (43.7 ng/mL in control, n = 16 vs 104.3 ng/mL in HFD, n = 17; P < .001) and significantly lower amounts of high-molecular-weight adiponectin (4.80 μg/mL in control, n = 16 vs 3.67 μg/mL in HFD, n = 18; P = .002) compared with the control group. Higher serum amyloid A levels in the HFD group (60.4 μg/mL in control, n = 17 vs 117.9 μg/mL in HFD, n = 18; P < .001) suggest inflammation in the HFD-induced obese animals. The HFD group had lower hepatic nonheme iron (3.12 μg/mg protein in control, n = 17 vs 0.869 μg/mg protein in HFD, n = 16; P < .001). Expression of hepcidin messenger RNA (mRNA) was only 54% of the control levels in HFD mice (P = .016). However, the ratio of hepcidin mRNA expression to nonheme iron was 2.5-fold higher in the HFD compared with the control animals. Hepcidin is a homeostatic regulator of iron metabolism that restricts intestinal iron absorption and is also known as a mediator of inflammation. Increased serum amyloid A levels and a higher ratio of hepatic hepcidin mRNA expression to nonheme iron suggest that lower hepatic iron status in obese animals might be associated with inflammation.