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

Abstract

Previously, we showed that high fat diet (HFD)‐induced obesity resulted in lower hepatic iron storage. To further investigate the effect of diet‐induced increase in adiposity on hepatic iron storage level and determine whether these obesity‐related changes could be reversed by decreasing fat mass through feeding a low fat diet, we compared hepatic iron levels in HFD‐induced obese mice after their diets were switched to a low fat diet with those continued to be fed HFD. Five‐week‐old female C57BL/6 mice were assigned to three groups – LL group was fed control diet containing 10% kcal fat for 31 weeks, HH group was fed HFD containing 60% kcal fat for 31 weeks, and HL group was fed HFD for the first 15 weeks and switched to the control diet for the following 16 weeks. Fat mass and lean body mass were measured by MRI at 14th and 30th weeks. To assess the hepatic iron storage, total iron content was measured by ICP‐MS and ferritin protein levels were determined by Western blot analysis. mRNA levels of hepatic hepcidin (Hamp) (the key factor which regulates body iron level) and hepatic and duodenal BMP‐6 (Bmp6) (a signaling molecule known to affect hepcidin expression) were determined by real time PCR. Body weights were significantly different among groups (35.8 ± 1.9 g, 40.6 ± 1.3 g, 63.1 ± 1.5 g in LL, HL, and HH groups, respectively). Fat mass was significantly different among groups (11.4 ± 2.0 g, 15.8 ± 1.0 g, 37.5 ± 1.1 g in LL, HL, and HH groups, respectively). Fat mass of HL group decreased from 19.0 ± 1.1 g at 14th wk to 15.8 ± 1.0 g at 30th wk. Total hepatic iron content of HL group was similar to that of LL group, which was about 30% higher than that of HH group (74.2 ± 7.5 μg/g tissue, 72.7 ± 2.6 μg/g tissue, 55.7 ± 3.8 μg/g tissue in LL, HL, and HH groups, respectively, p<0.05). Liver ferritin protein levels were similar in LL and HL groups, and significantly lower in HH group. These measures of iron status were significantly negatively correlated with body fat mass (r=−0.627, p<0.01 for liver iron content, r=−0.687, p<0.001 for ferritin). Liver Hamp mRNA level was not statistically different among groups. Liver Bmp6 expression was not significantly different among groups. In duodenum, however, Bmp6 mRNA level was significantly lower in HH group than LL and HL groups (p<0.01). Duodenal Bmp6 mRNA levels showed positive correlation with hepatic iron content (r=0.564, p<0.05) and hepatic Hamp expression (r=0.517, p<0.05). In summary, hepatic iron storage level is closely related to body adiposity. Reducing body fat mass through feeding a lower fat diet to HFD‐induced obese mice restores liver iron storage by lowering duodenal Bmp6 mRNA levels.Support or Funding InformationSupported by research funds through the Research Institute of Human Ecology (RIHE) in Seoul National University and USDA contract #58‐1950‐0‐014.