Abstract: BACKGROUND: Type 2 diabetes mellitus can induce liver inflammation, and exercises have been proved to improve type 2 diabetes mellitus, but the mechanism is unclear.
OBJECTIVE: To explore the effects of aerobic and resistance exercises on liver inflammation in type 2 diabetic rats.
METHODS: Sprague-Dawley male rats were randomly divided into six groups (n=8 per group), which were blank control group, aerobic exercise group, resistance exercise group, diabetic model group, diabetic aerobic exercise group, and diabetic resistance exercise group. Animal models of type 2 diabetes mellitus were established with high-sugar and high-fat diet combined with low-dose streptozotocin. The aerobic exercise was carried out on a non-weight-bearing treadmill, 20 m/min, 60 min/d, 5 days per week, for 8 weeks in total. The resistance exercise was set to be a weight-bearing ladder exercise, during which the load was progressively increased to 100% of the maximum load. The weight-bearing ladder exercise was repeated three times under the same load, a session per day, 5 days a week, for 8 weeks in total. Fasting blood glucose was measured by Johnson & Johnson blood glucose meter, and glucose tolerance test was performed by intraperitoneal injection, and the area under the blood glucose line (AUC) was calculated. Fasting insulin, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, caspase-1, and interleukin-1β were tested by enzyme-linked immunosorbent assay. The morphological changes of liver tissue were observed by hematoxylin-eosin staining.
RESULTS AND CONCLUSION: Compared with the blank control group, fasting blood glucose and AUC increased significantly in the diabetic model group (P < 0.01). After exercise intervention, fasting blood glucose and AUC in the diabetic aerobic exercise group and diabetic resistance exercise group were still significantly higher than those in the blank control group (P < 0.01, P < 0.05). However, compared with the diabetic model group, fasting blood glucose and AUC were significantly decreased in the diabetic aerobic exercise group and diabetic resistance exercise group (all P < 0.01), and fasting blood glucose and AUC in the diabetic resistance exercise group were significantly lower than those in the diabetic aerobic exercise group (P < 0.05). Compared with the blank control group, the structure of hepatic lobules was unclear and the arrangement of hepatocyte cords was disordered in the diabetic model group, accompanied by enlarged hepatocytes and inflammatory cell infiltration to varying degrees; the arrangement of hepatocytes was more regular, hepatocyte swelling was improved, and the number of inflammatory cells decreased in the diabetic aerobic exercise group; the arrangement of hepatocytes was irregular, hepatocyte swelling was slightly improved, and the number of inflammatory cells decreased in the diabetic resistance exercise group. The expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, caspase-1, and interleukin-1β in the liver of rats in the diabetic model group were significantly higher than those in the blank control group (P < 0.01), while the expression levels of these indicators in the diabetic aerobic exercise group were significantly lower than those in the diabetic model group (P < 0.05). Compared with the diabetic model group, the expression of the above-mentioned indicators showed a downward trend but did not change significantly in the diabetic resistance exercise group (P > 0.05), and there was also no significant difference between diabetic aerobic exercise group and diabetic resistance exercise group (P > 0.05). To conclude, aerobic exercise can effectively alleviate liver inflammations induced by diabetes, maybe because the aerobic exercise can reduce the activation of NLRP3 inflammasome and inhibit interleukin-1β expression, while the resistance exercise that can significantly improve hyperglycemia and insulin resistance has no obvious effect on liver inflammations induced by diabetes.

Key words: aerobic exercise, resistance exercise, type 2 diabetes mellitus, NLRP3, inflammation