Treadmill Exercise Attenuates High-Fat Diet-Induced Intestinal Mucosal Barrier Dysfunction and Pyroptosis in Mice
LIN Wei1, YUAN Shunling1, WU Jiyou2, GUO Weichang2*, QIU Liangwu2*
This study aimed to investigate the effects of treadmill exercise on intestinal mucosal barrier function and pyroptosis in high-fat diet-fed mice. C57BL/6J mice were randomly divided into a control group (WT group), a high-fat diet group (HFD group), and a high-fat diet plus exercise group (HFD-EX group). Mice in the HFD-EX group underwent treadmill exercise for 12 weeks. After the intervention, body mass was measured and plasma samples were collected for the determination of TG (triglycerides), TC (total cholesterol), HDL (high-density lipoprotein), and LDL (low-density lipoprotein) levels. Plasma DAO (diamine oxidase) and LPS (lipopolysaccharide) levels were determined by ELISA. Histopathological changes in ileal tissue were observed by HE (hematoxylin and eosin) staining. The expression of ZO-1 and occludin in ileal tissue was assessed by immunofluorescence, and the protein levels of NF-κB, NLRP3, Caspase-1, GSDMD, GSDMD-N, and IL-18 in ileal tissue were determined by Western blot. The results showed that treadmill exercise significantly reduced body mass and improved dyslipidemia in high-fat diet-fed mice, as evidenced by significant decreases in TG, TC, and LDL levels and a significant increase in HDL level (P<0.05, P<0.01). Meanwhile, treadmill exercise significantly decreased plasma DAO and LPS levels in high-fat diet-fed mice (P<0.05, P<0.01), attenuated ileal mucosal pathological injury, ameliorated abnormalities such as villus disorganization and thinning of the mucosal epithelium, significantly increased the percentage of fluorescence area for ZO-1 and occludin in ileal tissue (P<0.01), and markedly downregulated the protein expression levels of NF-κB, NLRP3, Caspase-1, GSDMD, GSDMD-N, and IL-18 (P<0.05, P<0.01). These findings indicate that treadmill exercise improves lipid metabolism disorders, attenuates ileal mucosal barrier injury, and inhibits activation of NF-κB/NLRP3-related pyroptotic signaling in high-fat diet-fed mice. Its protective effects may be associated with upregulation of tight junction protein expression, reduction of LPS translocation, and suppression of Caspase-1/GSDMD mediated pyroptosis-related processes.
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