Journal of Functional Foods (Dec 2022)
Butyrate ameliorates inflammation of alcoholic liver disease by suppressing the LPS-TLR4-NF-κB/NLRP3 axis via binding GPR43-β-arrestin2
Abstract
Alcoholic liver disease (ALD) regarding to liver damage caused by alcohol abuse is characterized by chronic liver inflammation, with dysregulations of the gut microbiota and its metabolites. Accumulating studies has demonstrated that butyrate exhibits pleitropic benefits in chronic metabolic diseases. The present study was designed to investigate the effects and mechanisms of butyrate on ALD. In vivo, C57BL/6J mice were fed with isocaloric modified Lieber-DeCarli liquid diets with or without ethanol which supplemented with sodium butyrate (NaB, 0.6 g/kg) for 6 weeks. In vitro, murine macrophage RAW264.7 were pretreated with NaB or G protein coupled receptor (GPR) 43 antagonist to verify the specific mechanism of NaB effectiveness in LPS-induced inflammatory response. Finally, the routine indexes indicated that NaB treatment significantly alleviated liver injury and lipid deposition, as well as inflammation in ALD mice. On the other hand, M2 macrophage (Mψ) along with its representative enzyme Arg-1, were significantly elevated, whereas M1 Mψ coupled with its marker enzyme iNOS, showed decreased after NaB intervention. Moverover, the expressions of Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), nod-like receptor protein 3 (NLRP3) and caspase-1 were notably decreased with NaB intervention. Intriguingly, the inhibition of GPR43 signals impaired the anti-inflammation effects of NaB. And our further research found that NaB supplementation not only increased the expressions of GPR43 and β-arrstine2 (ARRB2), but also strengthened the interactions between ARRB2 and NLRP3/TAK1 binding protein 1 (TAB1). These results indicated that butyrate may ameliorate ALD by means of modulating Mψ polarization and suppressing LPS-TLR4-NF-κB/NLRP3 axis via mediating GPR43-ARRB2 signaling pathway.
