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

Abstract

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.

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Fig. 1
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Abbreviations

ADFI :

average daily feed intake

ADG :

average daily gain

ADII :

average daily iron intake

Con:

control

DMT1 :

divalent metal transporter

FPN :

ferroportin

FTH:

ferritin heavy chain

FTL :

ferritin light chain

HGB :

hemoglobin

RS:

restraint stress

TS :

transferrin saturation

TIBC :

total iron-binding capacity

TF :

transferrin

Tf-Fe :

transferrin-bound iron

TFR1 :

transferrin receptor 1

TFR2 :

transferrin receptor 2

UIBC :

unsaturated iron-binding capacity

ZIP14 :

zrt/irt-like protein 14

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Funding

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.

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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.

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Correspondence to Wenqiang Ma.

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Cite this article

Guo, S., Yang, C., Jiang, S. et al. Repeated Restraint Stress Enhances Hepatic TFR2 Expression and Induces Hepatic Iron Accumulation in Rats. Biol Trace Elem Res 196, 590–596 (2020). https://doi.org/10.1007/s12011-019-01956-4

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Keywords

  • Repeated restraint stress
  • Hepatic iron accumulation
  • TFR2
  • Rats