Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways [I]

Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron–sulfur (Fe–S) cluster synthesis. Heme and Fe–S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways—gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule. Male C57BL/6J mice of 6 weeks of age were fed with a control diet (Control;10% kcal fat), a high-fat diet (HF; 60% kcal fat), or a high-fat diet supplemented with 0.023% (w/w) sodium ferrous citrate (HF+SFC) for 15 weeks. Control diet (D12450B) contained 10 kcal% fat, 20 kcal% protein, and 70 kcal% carbohydrate, whereas the HF diet (D12492) contained 60 kcal% fat, 20 kcal% protein, and 20 kcal% carbohydrate (Research Diets, Inc., New Brunswick, NJ, USA). For each group, a mix of all sample cDNAs was used.