Abstract
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.
Highlights
Activation of Adenosine 5′-monophosphate-activated protein kinase/Sirtuin1 (AMPK/SIRT1) exerts an effect in alleviating obesity and gut damage
The results showed that colon length was decreased, intestinal permeability was increased, and content of colonic inflammatory factor Interleukin- 6 (IL-6) was increased in high-fat diet (HFD)-fed mice compared with normal diet (ND)-fed mice, while all the damage was ameliorated by Sodium nitroprusside (SNP) (Fig. 3A-D)
Our results showed that SNP restored LPS-induced loss of the tight junction proteins Zonula occludens 1 (ZO-1) and occludin in Caco-2 cell monolayers, and restored HFD induced loss of the tight junction proteins ZO-1 and Occludin in mice, which reversed the increased intestinal barrier permeability
Summary
SNP 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. AMPKα/SIRT1 pathway and gut barrier indicators were investigated
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