摘要
Gut microbiota-derived propionate has been shown to ameliorate alcoholic liver disease(ALD)through modulating gut-liver axis in our previous study.However,the underlying mechanism remains unclear.In this study,we synthesized propionylated high-amylose maize starch(HAMSP)to achieve gut-targeted delivery of propionate,evaluated its therapeutical potential against ALD compared with oral sodium propionate,and elucidated its mechanism targeting the gut-liver axis.Animal experiments demonstrated that HAMSP outperformed oral sodium propionate in improving liver function,attenuating liver steatosis,reducing liver oxidative stress and inflammation in ALD mice.Mechanistic investigations revealed that depletion of propionate receptors GPR41 and GPR43 blocked the protective effects of HAMSP against ALD.In ALD mice,the activation of GPR41/43 triggered by HAMSP stimulated IL-22 production,leading to STAT3 phosphorylation,which enhanced the gut barrier integrity and suppressed LPS translocation,thereby restoring the gut-liver axis homeostasis.These findings were further corroborated in Caco-2 cells.In summary,this study provided novel evidence that propionate regulates gut-liver axis homeostasis in ALD via the GPR41/43-IL-22-STAT3 signaling pathway.It also establishes scientific foundation for the therapeutic application of HAMSP,a gut-targeted propionate delivery agent,in ALD prevention and treatment.
基金
supported by the Shandong Provincial Natural Science Foundation(Grant No.ZR2022QH051)
the National Natural Science Foundation of China(Grant No.82204325,82304430 and 82404568)
Science,Education and Industry Integration Innovation Pilot Project from Qilu University of Technology(Grant No.2025YSZX01).
