Regulation of a High-Iron Diet on Lipid Metabolism and Gut Microbiota in Mice

Iron homeostasis disorder is associated with the imbalance of lipid metabolism, while the specific interaction remains unclear. In the present study, we investigated the effect of a high-iron diet on lipid metabolism in mice. The C57BL/6 mice were fed with a normal diet (WT) or a high-iron diet (WT + Fe) for 12 weeks. We found that mice in the WT + Fe group showed a significant decrease in body weight gain, body fat and lipid accumulation of liver when compared with mice in the WT group. Accordingly, serum total cholesterol and triglyceride levels were both reduced in mice with a high-iron diet. Moreover, mice in the WT + Fe group exhibited a significant decrease in expression of genes regulating adipogenesis and adipocyte differentiation, and a significant increase in expression of fat hydrolysis enzyme genes in both liver and adipose tissues, which was consistent with their dramatic reduction in adipocyte cell size. In addition, a high-iron diet decreased the relative abundance of beneficial bacteria (Akkermansia, Bifidobacterium and Lactobacillus) and increased the relative abundance of pathogenic bacteria (Romboutsia and Erysipelatoclostridium). Thus, our research revealed that a high-iron diet reduced lipid deposition by inhibiting adipogenesis and promoting lipolysis. Altered gut microbial composition induced by a high-iron diet may not play a critical role in regulating lipid metabolism, but might cause unwanted side effects such as intestinal inflammation and damaged villi morphology at the intestinal host-microbe interface. These findings provide new insights into the relationship among iron, lipid metabolism and gut microbiota.