Effect of aerobic exercise on GRP78 and ATF6 expressions in mice with non-alcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a prevalent medical condition with an ever-growing trend. Although multiple intracellular mechanisms are involved, endoplasmic reticulum (ER) stress has been demonstrated to play a significant role in the genesis and progression. Most of the research supports the advantages of exercise for NAFLD. However, little is known about the molecular mechanism(s) that underpin the effectiveness of exercise training in NAFLD. This study aimed to identify how aerobic exercise affected hepatic ER stress in a mouse NAFLD model. In this study, the mice were fed either a standard diet (SD) or a high-fat diet (HFD) for 17 weeks. HFD mice were trained on a treadmill during the last eight weeks. All animals were tested for serum levels of biochemical assays, protein expression, and gene expression. The hematoxylin and eosin, Oil red O, and immunohistochemistry staining were also performed. The results indicated that a high-fat diet generated NAFLD, with serum lipid disruption and hepatic function impairment, and increased GRP78 and ATF6 expressions. However, aerobic training reversed the majority of these alterations. It is concluded that NAFLD appears to be associated with hepatic ER stress response, and aerobic exercise mitigates NAFLD via lowering ER stress proteins GRP78 and ATF6.

Keywords

Endoplasmic reticulum stress / Exercise / GRP78 / ATF6 / Nonalcoholic fatty liver disease

Ethical approval statement

The animals were housed at a controlled room temperature (25 ​± ​1) °C, relative humidity (50%-60%), and a light/dark cycle of 12/12 ​h. Food and water were provided ad libitum during experimental period. All procedures were performed in accordance with the guidelines established by the Animal Care and Committee Guidelines of Chengdu Sport University.

Authors’ contributions

JHL had conceived, carried out the experiments and wrote the manuscript. LH had revised and edited the manuscript. WX and CG had reviewed the manuscript. SLZ and XLX had analyzed the data. All authors have read and agreed to the published version of the manuscript.

Conflict of interest

The authors of this paper declare that they have no direct or indirect interests that are in direct conflict with the conduction of the study.

Acknowledge statement

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Funding

This work was provided by the National Natural Science Foundation of China(31900846)

the Science and Technology Program of Sichuan, China(2020YFS0436). We would like to thank Jiaqian Wang)

the Science and Technology Program of Sichuan, China(Yalong Li)

the Science and Technology Program of Sichuan, China(Changjun Jiang who assisted in performing daily training of the mice over the course of the study)