Lower hepatic iron storage associated with obesity in mice can be restored by decreasing body fat mass through feeding a low-fat diet

Authors: CHUNG, HAK - Seoul National University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SMITH, DONALD - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HAN, SUNG NIM - Seoul National University

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2016
Publication Date: 9/12/2016
Citation: Chung, H., Wu, D., Smith, D.E., Meydani, S.N., Han, S. 2016. Lower hepatic iron storage associated with obesity in mice can be restored by decreasing body fat mass through feeding a low-fat diet. Nutrition Research. 36(9):955-963. https://doi.org/10.1016/j.nutres.2016.06.003.

Interpretive Summary: Studies suggest that obesity may be associated with a higher prevalence of iron deficiency. For example, the prevalence of iron deficiency among obese or overweight children and adolescents is higher compared to those of normal weight. However, there has not been consistent information available regarding whether these obesity-related changes in iron status could be reversed by reducing body fat. Using an animal model in this study, we tested the hypothesis that the obesity-related changes in iron status in the liver could be reversed by decreasing body fat through feeding a low fat diet. Our results showed that mice fed a high fat diet for 15 weeks greatly increased their body weight and fat mass compared to those fed a low fat diet. The group of mice fed a high fat diet but were switched to low fat diet (HL) for the next 16 weeks had weight loss and reduced fat mass while the group that continued high fat diet (HH) showed further increase in weight and fat mass. The liver iron concentration in the low fat diet group was 30% higher than that in the high fat diet group. In investigating the mechanisms underlying the altered iron status associated with obesity, we found the changes in a few molecules that regulate iron transport and storage were correlated with obesity status. Thus, our study suggests that obesity causes loss of iron from the liver and that reducing body weight and fat mass by altering the diet could restore liver iron storage. This information will assist doctors in the treatment of obesity-associated iron deficiency.

Technical Abstract: High-fat diet (HFD)-induced obesity has been reported to result in low hepatic iron storage. In the current study, we tested the hypothesis that these obesity-related changes in hepatic iron status could be reversed by decreasing adiposity by feeding a low-fat diet. Five-week-old C57BL/6 mice were assigned to three groups: the LL group was fed a control diet for 31 weeks, the HH group was fed a HFD for 31 weeks, and the HL group was fed the HFD for 15 weeks and then switched to the control diet for 16 weeks. The fat mass of the HL group decreased by 3.2 g from the 14th to the 30th week. Fat mass was significantly different among the groups (11.4, 15.8, and 37.5 g in the LL, HH, and HL groups, respectively; P<0.001). The liver iron concentration of the HL group was similar to that of the LL group, which was about 30% higher than that of the HH group (74.2, 72.7, and 55.7 micrograms/g in the LL, HL, and HH groups, respectively; P<0.05). Duodenal cytochrome b (Dcytb) messenger RNA (mRNA) levels were higher in the HL group than in the HH group. Although bone morphogenetic protein 6 (Bmp6) mRNA levels showed no significant differences in the liver, duodenal Bmp6 mRNA levels were significantly lower in the HH group compared with the LL and HL groups. Liver Smad1/5 proteins were differentially activated: the HH group had significantly less phosphorylated Smads than did the LL and HL groups. Our data demonstrate that hepatic iron storage levels are closely related to body adiposity, and reducing body fat mass through feeding a lower-fat diet to HFD-induced obese mice restores liver iron storage.