Effect of Different Exercise Intensities on Hepatocyte Apoptosis in HFD-Induced NAFLD in Rats: The Possible Role of Endoplasmic Reticulum Stress through the Regulation of the IRE1/JNK and eIF2/CHOP Signal Pathways.

OBJECTIVE

To investigate the impact of different-intensity exercise on lipid metabolism, oxidative stress, hepatocyte injury, and apoptosis and the related protein expression of endoplasmic reticulum stress on nonalcoholic fatty liver disease rats.

METHOD

50 male Sprague-Dawley rats, 2 months old, were randomly divided into the normal control (CON) group, high-fat diet (HFD) group, low-intensity exercise (LIE) group, moderate-intensity exercise (MIE) group, and incremental-intensity exercise (IIE) group. Blood lipids were tested by the automatic biochemical analyzer. The changes in liver tissues were observed by hematoxylin-eosin staining (HE). The protein expression of Bax and Bcl-2 was detected by the immunohistochemical method. The apoptosis of hepatocytes was detected by the TUNEL method. The protein expression of GRP78, Caspase-3, IRE1, p-IRE1, JNK1, CHOP, PERK, eIF2, and ATF4 was detected by Western blotting.

RESULTS

Our study showed that compared with the HFD group, TG, TC, FFA, and LDL-c were reduced in all exercise groups. The different exercise intensities could reduce the protein expression of ATF4, Bax, and hepatocyte apoptosis. Meanwhile, the antioxidant function and Bcl-2 were increased. However, the moderate-intensity exercise demonstrated more effect on improving the antioxidant capacity and inhibiting hepatocyte apoptosis. Compared with the HFD group, Caspase-3 and JNK were significantly decreased in all exercise groups ( < 0.01) and CHOP was decreased in the LIE and MIE groups ( < 0.05). IRE1, eIF2, the ratio of p-IRE1/IRE1 ( < 0.01), and ATF4 were decreased ( < 0.05) in the MIE group. Compared with the IIE group, p-IRE1 was decreased ( < 0.05) in the MIE group. GRP78 had no significant difference among the exercise groups.

CONCLUSION

Exercise at different intensities improved blood lipid and hepatic injury in NAFLD rats. However, the body weight of the rats in each exercise group was not significantly different. Moderate-intensity exercise demonstrated more effect on improving the antioxidant ability and inhibiting hepatocyte apoptosis. The possible mechanism depends on the regulation of endoplasmic reticulum stress signaling pathways IRE1/JNK and eIF2/CHOP.