Discussion
inflammation, liver injury, metabolic diseases, Diabetes, pre-diabetic, diabetes
INFILTRATION, INFLAMMATION, METABOLIC DISEASES, INSULIN RESISTANCE, DIABETES, PRE-DIABETIC, PRE-DIABETES, PATHOLOGY, INSULIN SENSITIVITY, DIABETES
In this study, for the first time according to our knowledge, we found that 6-month combined Yijingjing and resistance training was able to alleviate systemic insulin resistance and liver injury, and inhibit the overactivation of NLRP3 inflammasome in pre-diabetic elderly subjects. More important, the NLRP3 inflammasome was positively correlated with systemic insulin sensitivity and liver injury.Diabetes has long been associated with a chronic low-grade inflammatory state but its precise mechanisms remain unclear. In the past decade, the role of NLRP3 inflammasome in diabetes has been greatly appreciated, as the chronic low-grade inflammatory state accompanied by diabetes is at least partially consequent to the activation of NLRP3 inflammasome (It is well established that physical exercise is an effective way to counteract diabetes but its mechanisms are not clear. Of note, in 2011, Vandanmagsar (Additionally, we also observed significant alleviation of whole body insulin resistance and liver injury after the exercise intervention, however, whether the improvement of insulin sensitivity and liver function by combined Yijinjing and resistance training intervention is associated with the reduced expression of NLRP3 inflammasome remains unknown. Previous studies have shown that the liver is not only a central organ of energy metabolism, but also acts as an immune organ (The potential mechanisms by how exercise alleviates insulin resistance and liver injury through NLRP3 inflammasome.To sum up, we speculated that the combined Yijinjing and resistance training may be an effective strategy to inhibit the robust NLRP3 inflammasome activation, thereby alleviating liver injury and insulin resistance in pre-diabetes. Apart from this mechanism, the combined Yijinjing and resistance training may also alleviate liver injury, reduce the release of harmful DAMPs from injured hepatocytes, thereby inhibiting the overactivation of NLRP3 inflammasome (Apart from liver, the skeletal muscle is another major metabolic organ. Moreover, increasing evidence suggests that inflammation occurs in skeletal muscle is mainly manifested by increased immune cell infiltration and proinflammatory activation. By secreting proinflammatory molecules, the immune cells may induce inflammation and insulin resistance in skeletal muscle (Strengths of our study include the objects of study, intervention protocol. The objects of our study are pre-diabetic populations. Although it is wise to ameliorate diabetes by developing an effective strategy for the pre-diabetes, no RCTs are available to evaluate the effects of Yijinjing in patients with metabolic diseases such as pre-diabetes. Since data from long-term studies that show the effects of combined Yijinjing and resistance training on pre-diabetic are currently lacking, the findings from our study may have significant clinical implications for diabetes because they show that if healthy lifestyle intervention is established at the early stage of diabetes they can prevent diabetes progression.Our studies have some limitations. First, the sample size of this study is relatively small and thus may not be fully representative of the general pre-diabetic elderly population, therefore, randomized controlled studies with larger sample sizes are needed to confirm these findings in the future. In order to obtain accurate information regarding the degree of inflammation and liver pathology, liver biopsies would be needed. However, given the ethical issues, it is hard to obtain biopsies from patients, thus limiting the direct measurement. Additionally, in this manuscript, we combined the data from males and females. For precision medicine, it would be meaningful to study the function of exercise training in males and females separately. Lastly, although we found positive correlations between insulin resistance, liver pathology and NLRP3 inflammasome, however, it should be noted that correlation does not imply causation. Therefore, more research including mouse model is needed to define the role of NLRP3 inflammasome in pre-diabetic populations in the future.