Dietary Iron Modulates Glucose and Lipid Homeostasis in Diabetic Mice
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Imbalance of iron homeostasis has been involved in clinical courses of metabolic diseases such as type 2 diabetes mellitus, obesity, and nonalcoholic fatty liver, through mechanisms not yet fully elucidated. Herein, we evaluated the effect of dietary iron on the development of diabetic syndromes in genetically obese db/db mice. Mice (aged 7 weeks) were fed with high-iron (HI) diets (1000 mg/kg chow) or low-iron (LI) diets (12 mg/kg) for 9 weeks. HI diets increased hepatic iron threefold and led to fourfold higher mRNA levels of hepcidin. HI also induced a 60% increase in fasting glucose due to insulin resistance, as confirmed by decreased hepatic glycogen deposition eightfold and a 21% decrease of serum adiponectin level. HI-fed mice had lower visceral adipose tissue mass estimated by epididymal and inguinal fat pad, associated with iron accumulation and smaller size of adipocytes. Gene expression analysis of liver showed that HI diet upregulated gluconeogenesis and downregulated lipogenesis. These results suggested that excess dietary iron leads to reduced mass, increased fasting glucose, decreased adiponectin level, and enhancement of insulin resistance, which indicated a multifactorial role of excess iron in the development of diabetes in the setting of obesity.
KeywordsDietary iron Diabetic mice Glycolipid metabolism Type 2 diabetes mellitus Obesity
This study was supported by the Natural Science Foundation of Zhejiang province of China (LR16C170001), National Natural Science Foundation of China (31572411), and Major Science and Technology Project of Zhejiang province (2015C02022).
Compliance with Ethical Standards
All experimental procedures were approved by the institutional ethics committee of Zhejiang University.
Conflict of Interest
The authors declare that they have no conflict of interest.
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