Exercise training-attenuated insulin resistance and liver injury in elderly pre-diabetic patients correlates with NLRP3 inflammasome

• Published in: Frontiers in immunology Vol. 14; p. 1082050
• Main Authors: Zhang, Tan, Tian, Jingjing, Fan, Jingcheng, Liu, Xiangyun, Wang, Ru
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01.02.2023
• Subjects: Aged; exercise training; Humans; Immunology; Inflammasomes - metabolism; Insulin Resistance; Liver - metabolism; liver injury; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; pre-diabetes; Prediabetic State; liver injury; pre-diabetes; NLRP3 inflammasome; insulin resistance; exercise training
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1082050

Diabetes is one of the most common metabolic diseases and continues to be a leading cause of death worldwide. The NLRP3 inflammasome has been shown to exert detrimental effects on diabetic models. However, evidence linking NLRP3 inflammasome and pre-diabetes has been scarcely explored. Herein, we aimed to determine whether the NLRP3 inflammasome correlates with insulin resistance and liver pathology in a cohort of pre-diabetic subjects. 50 pre-diabetic subjects were randomly assigned to a Pre-diabetes Control (DC, n=25) and a Pre-diabetes exercise (DEx, n=25) group. 25 Normal subjects (NC) were selected as controls. The DEx group performed a 6-month combined Yijingjing and resistance training intervention, while DC and NC group remained daily routines. Clinical metabolic parameters were determined with an automatic biochemistry analyzer; inflammatory cytokines were quantified by the ELISA assay; the protein expressions of NLRP3 inflammasome components in PBMCs were evaluated by Western Blot. The insulin resistance, liver injury and NLRP3 inflammasome activity were higher in pre-diabetic individuals than in normal control group. However, 6-month exercise intervention counteracted this trend, significantly improved insulin sensitivity, reduced liver injury and inhibited the overactivation of NLRP3 inflammasome in pre-diabetic subjects. Moreover, positive correlations between insulin resistance, liver pathology and NLRP3 inflammasome were also found. Our study suggests that exercise training is an effective strategy to alleviate insulin resistance and liver injury in elderly pre-diabetic subjects which is probably associated with the inhibition of NLRP3 inflammasome activity.