Repeated Restraint Stress Enhances Hepatic TFR2 Expression and Induces Hepatic Iron Accumulation in Rats

  • Shihui Guo
  • Chun Yang
  • Shuxia Jiang
  • Yingdong Ni
  • Ruqian Zhao
  • Wenqiang MaEmail author


Abnormal hepatic iron metabolism is detrimental to health. The objective of this study was to detect repeated restraint stress on liver iron metabolism in rats. Twenty-four male rats aged 7 weeks were randomly divided into 2 groups: control group (Con) and repeated restraint stress group (RS). Rats were subjected to 6 h of daily restraint stress for 14 consecutive days in the repeated restraint stress group. The results showed that repeated restraint stress exposure decreased growth performance including impaired final weight (P = 0.07), reducing average daily gain (P = 0.01), and average daily feed intake (P = 0.00) during the 14-day experimental period. Repeated restraint stress exposure did not affect hemoglobin content and plasma iron parameters except downregulated unsaturated iron-binding capacity (P = 0.04). Repeated restraint stress exposure inhibited liver development (P = 0.03) and induced liver iron accumulation (P = 0.05). In addition, repeated restraint stress downregulated the expression of transferrin (TF) and transferrin receptor 2 (TFR2) at the mRNA level (P < 0.01), but upregulated at the protein level (P = 0.03 for TF; P = 0.00 for TFR2). These results indicated that repeated restraint stress induces hepatic iron accumulation, which is closely related to higher expression of hepatic TFR2 protein in rats.


Repeated restraint stress Hepatic iron accumulation TFR2 Rats 



average daily feed intake


average daily gain


average daily iron intake




divalent metal transporter




ferritin heavy chain


ferritin light chain




restraint stress


transferrin saturation


total iron-binding capacity




transferrin-bound iron


transferrin receptor 1


transferrin receptor 2


unsaturated iron-binding capacity


zrt/irt-like protein 14


Author Contributions

Ruqian Zhao, Yingdong Ni, and Wenqiang Ma conceived the project. Shihui Guo and Chun Yang carried out most experiments. Shuxia Jiang assisted animal experiment. Wenqiang Ma wrote the manuscript. The final version of the manuscript is approved by all co-authors.

Funding Information

This work was supported by grants from the National Key Research and Development Program of China (2016YFD0500502); the National Natural Science Foundation of China (31872439); the Priority Academic Program Development of Jiangsu Higher Education Institutions; and the Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Authors and Affiliations

  1. 1.Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary MedicineNanjing Agricultural UniversityNanjingPeople’s Republic of China
  2. 2.MOE Joint International Research Laboratory of Animal Health & Food SafetyNanjing Agricultural UniversityNanjingPeople’s Republic of China

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