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

SIMPLE SUMMARY: Iron is an essential micronutrient involved in many important physiological activities and plays a key role in growth and development of animals. However, exposure to high levels of dietary iron has an effect on growth performance, lipid metabolism, and gut microbiota in animals. In this study, we evaluated the effects of a high-iron diet on lipid metabolism and gut microbiota in mice. Our study shows that a high-iron diet decreased fat accumulation and lipid deposition by downregulating adipogenesis and upregulating lipolysis in the liver and adipose tissues of mice. In addition, a high-iron diet induced slight intestinal damage with duodenal inflammation, and reshaped the gut microbiota, but the role of gut microbiota in regulating lipid metabolism needs to be further explored. Hence, this study shows that a high-iron diet can negatively affect mice health, and it is recommended to strictly control the intake of iron in livestock and poultry. ABSTRACT: 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.