PDF(Pubmed)
Abstract：
Iron deficiency is the number one nutritional problem worldwide. Iron uptake is regulated at the intestine and is highly influenced by the gut microbiome. Blood from the intestines drains directly into the liver, informing iron status and gut microbiota status. Changes in either iron or the microbiome are tightly correlated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD). To investigate the underlying mechanisms of the development of MASLD that connect altered iron metabolism and gut microbiota, we compared specific pathogen free (SPF) or germ-free (GF) mice, fed a normal or low-iron diet. SPF mice on a low-iron diet showed reduced serum triglycerides and MASLD. In contrast, GF low-iron diet-fed mice showed increased serum triglycerides and did not develop hepatic steatosis. SPF mice showed significant changes in liver lipid metabolism and increased insulin resistance that was dependent upon the presence of the gut microbiota. We report that total body loss of mitochondrial iron importer Mitoferrin2 (Mfrn2-/-) exacerbated the development of MASLD on a low-iron diet with significant lipid metabolism alterations. Our study demonstrates a clear contribution of the gut microbiome, dietary iron, and Mfrn2 in the development of MASLD and metabolic syndrome.
摘要：
缺铁是全球头号营养问题。铁的摄取在肠道受到调节，并受到肠道微生物组的高度影响。肠道的血液直接流入肝脏,告知铁状态和肠道微生物群状态。铁或微生物组的变化与代谢功能障碍相关的脂肪变性肝病（MASLD）的发展密切相关。探讨铁代谢改变与肠道菌群连接的MASLD发育的潜在机制,我们比较了无特定病原体（SPF）或无菌（GF）小鼠，正常或低铁饮食。低铁饮食的SPF小鼠显示血清甘油三酯和MASLD降低。相比之下,GF低铁饮食喂养的小鼠显示血清甘油三酯增加，并且没有发生肝性脂肪变性。SPF小鼠显示肝脏脂质代谢的显着变化和胰岛素抵抗的增加，这取决于肠道微生物群的存在。我们报告说，在低铁饮食中，线粒体铁进口商Mitoferrin2（Mfrn2-/-）的全身丢失加剧了MASLD的发展，并伴有明显的脂质代谢改变。我们的研究表明，肠道微生物组有明显的贡献，膳食铁，和Mfrn2在MASLD和代谢综合征的发展中的作用。
