Abstract: Objective To investigate the therapeutic effect of mechanical loading on obesity and non-alcoholic fatty liver disease. Methods Thirty 6-week-old female C57BL/6 mice (body weight 18 g) were randomly assigned into three groups: normal control group (NC group, n=10), high-fat diet group (HF group, n=10) and high-fat diet with mechanical loading treatment group (HF+L group, n=10). All mice except for NC group were fed with high-fat diet for 12 weeks. After 6 weeks of high-fat diet, mice of HF+L group received 6-week mechanical loading. The whole body composition was analyzed to detect the total body fat content. The mesenteric fat, perirenal fat, inguinal fat, periuterine fat and the liver were collected and weighed. A portion of the liver sample was isolated for histological analysis (Oil red O staining and HE staining) to observe pathologic changes, while the other was used for Western blot assay to detect the expression of eIF2α, p-eIF2α and ATF4, which were the marker proteins of endoplasmic reticulum stress. Results Compared with the NC group, high-fat diet resulted in a significant increase in body weight and body fat (P＜0.05). After mechanical loading treatment, the body weight and body fat were significantly decreased in the HF+L group compared with those of HF group (P＜0.05). Hepatic histological analysis showed that high-fat diet induced hepatic steatosis, which was effectively alleviated by mechanical loading treatment (P＜0.05). Western blot analysis indicated that high-fat diet led to higher expression levels of p-eIF2α and ATF4 in liver, and mechanical loading was effective in inhibiting the increased expressions of p-eIF2α and ATF4.Conclusion Mechanical loading can effectively alleviate obesity and non-alcoholic fatty liver disease caused by high-fat diet, and its effects may be associated with endoplasmic reticulum stress in liver

Key words: obesity, fatty liver, activating transcription factor 4, mice, inbred C57BL, endoplasmic reticulum stress, mechanical loading, eukaryotic initiation factor 2α