HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway

Fatty liver can be induced by dietary habits and lifestyle and is directly related to obesity. Although the benefits of exercise interventions for reduction of liver fat have recently been acknowledged, the underlying mechanisms remain unclear. Thus, our present study investigated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on high-fat diet-induced hepatic lipid accumulation, and explored the role of endoplasmic reticulum (ER) stress signaling pathways. To establish an obesity model, rats were fed with a normal standard diet or a high-fat diet (45% kcal as fat). Then, both lean and obese rats were divided into three subgroups: sedentary control (LC, OC) groups, high-intensity interval training (LHI, OHI) groups, and moderated-intensity continuous training (LMI, OMI) groups (n = 10). Rats in the exercise group underwent a swimming training protocol for 8 weeks. After the experimental period, serum and liver tissues from different groups were dissected for morphological and biochemical analyses. The results showed that with HIIT and MICT interventions, body weight and serum inflammatory markers (e.g., MCP-1, IL-1β, and TNF-α) were reduced in obese rats. Interestingly, HIIT was more effective in ameliorating liver triglyceride content and enhancing mitochondrial metabolic-enzymatic activity than was MICT in obese rats. Both HIIT and MICT conferred beneficial properties through upregulating Nrf2 expression, improving antioxidant enzyme activities and reduction of hepatic ER stress, which may have been regulated by the Bip-mediated PERK-ATF4-CHOP pathway. In conclusion, our findings confirmed the effectiveness of HIIT and MICT, particularly HIIT, in mitigating hepatic lipid accumulation. (AU)

HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway.

Fatty liver can be induced by dietary habits and lifestyle and is directly related to obesity. Although the benefits of exercise interventions for reduction of liver fat have recently been acknowledged, the underlying mechanisms remain unclear. Thus, our present study investigated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on high-fat diet-induced hepatic lipid accumulation, and explored the role of endoplasmic reticulum (ER) stress signaling pathways. To establish an obesity model, rats were fed with a normal standard diet or a high-fat diet (45% kcal as fat). Then, both lean and obese rats were divided into three subgroups: sedentary control (LC, OC) groups, high-intensity interval training (LHI, OHI) groups, and moderated-intensity continuous training (LMI, OMI) groups (n = 10). Rats in the exercise group underwent a swimming training protocol for 8 weeks. After the experimental period, serum and liver tissues from different groups were dissected for morphological and biochemical analyses. The results showed that with HIIT and MICT interventions, body weight and serum inflammatory markers (e.g., MCP-1, IL-1ß, and TNF-α) were reduced in obese rats. Interestingly, HIIT was more effective in ameliorating liver triglyceride content and enhancing mitochondrial metabolic-enzymatic activity than was MICT in obese rats. Both HIIT and MICT conferred beneficial properties through upregulating Nrf2 expression, improving antioxidant enzyme activities and reduction of hepatic ER stress, which may have been regulated by the Bip-mediated PERK-ATF4-CHOP pathway. In conclusion, our findings confirmed the effectiveness of HIIT and MICT, particularly HIIT, in mitigating hepatic lipid accumulation.

Effects of different exercise on liver lipid accumulation and FGF21 secretion in obese rats / 中国应用生理学杂志

Objective: To investigate the effects of continuous exercise training (CT) and high-intensity interval exercise training (HIIT) on liver lipid metabolism and the correlation of the level of fibroblast growth factor 21(FGF21) in serum and liver tissues. Methods: Male SD rats were randomly divided into normal diet group (N) and obesity model group (H) after 1 week of adaptive feeding. Rats in the obesity model group were fed with 45% high-fat diet for about 8 weeks, and 20% weight increase compared with normal rats was considered as obesity. The rats were divided into normal diet control group (LC), normal diet HIIT group (LHI), normal diet CT group (LCT), High fat diet-induced obese control group (OC), obese HIIT group (OHI), and obese CT group (OCT) (n=10). Exercised rats were given weight-bearing swimming training intervention for 8 weeks. Blood samples were collected at least 24h after the last exercise intervention to detect the serum levels of inflammatory factors and FGF21. Liver tissue samples were collected to detect the lipid content, lipid metabolic enzyme content and FGF21 expression level. Results: Compared with LC group, the body weight, serum inflammatory factors levels and hepatic triglyceride content were increased significantly (P＜0.05). Hepatic triglyceride content was downregulated in LHI group and FGF21 expression level was enhanced in LCT group (P＜0.05). Compared with OC group, the body weight and hepatic triglyceride content were decreased significantly (P＜0.05), mitochondrial CPT-1β and β-HAD enzyme contents in liver were increased significantly (P＜0.05) in OHI group, the contents of LPL and FAT/CD36 enzyme in liver and the levels of FGF21 in serum and liver of OCT group were increased significantly (P＜0.05). Conclusion: Both exercise modes can reduce the body weight in normal and obese rats, and lipid deposition in the liver of obese rats. HIIT has a more significant effect on alleviating liver lipid deposition in obese rats by upregulating mitochondrial lipid oxidation level in normal and obese rats. CT improves the levels of FGF21 in serum and liver tissues of normal and obese rats, enhances enzyme contents that involved in fatty acids uptake to the liver, which has limited effect on alleviating lipid deposition in liver of obese rats.