Sodium nitroprusside protects HFD induced gut dysfunction via activating AMPKα/SIRT1 signaling

BMC Gastroenterology

Chen Li¹  Ting Liu¹  Zhihua Liu¹  Xiaomei Li¹  Yuanqi Li¹  Cong Liu¹  Xue Liang¹ 

[1] Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, Innovation Center for Advanced Interdisciplinary Medicine, The Fifth Affiliated Hospital of Guangzhou Medical University, 510700, Guangzhou, China;

关键词: AMPKα/SIRT1 signaling;    NO;    SNP;    Intestinal barrier dysfunction;    HFD;    Gut microbiota dysbiosis;   

DOI  :  10.1186/s12876-021-01934-y

来源: Springer

【 摘 要 】

BackgroundActivation of Adenosine 5′-monophosphate-activated protein kinase/Sirtuin1 (AMPK/SIRT1) exerts an effect in alleviating obesity and gut damage. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, has been reported to activate AMPK. This study was to investigate the effect of SNP on HFD induced gut dysfunction and the mechanism.MethodsSNP was applied on lipopolysaccharide (LPS) stimulated Caco-2 cell monolayers which mimicked intestinal epithelial barrier dysfunction and HFD-fed mice which were complicated by gut dysfunction. Then AMPKα/SIRT1 pathway and gut barrier indicators were investigated.ResultsSNP rescued the loss of tight junction proteins ZO-1 and occludin, the inhibition of AMPKα/SIRT1 in LPS stimulated Caco-2 cell monolayers, and the effects were not shown when AMPKa1 was knocked-down by siRNA. SNP also alleviated HFD induced obesity and gut dysfunction in mice, as indicated by the decreasing of intestinal permeability, the increasing expression of ZO-1 and occludin, the decreasing levels of pro-inflammatory cytokine IL-6, and the repairing of gut microbiota dysbiosis. These effects were complicated by the increased colonic NO content and the activated AMPKα/SIRT1 signaling.ConclusionsThe results may imply that SNP, as a NO donor, alleviates HFD induced gut dysfunction probably by activating the AMPKα/SIRT1 signaling pathway.

【 授权许可】

CC BY