A novel Fucose-specific lectin from Morchella esculenta modulates gut-liver Axis to alleviate non-alcoholic fatty liver disease.

Abstract

Morchella esculenta is an underexplored source of lectins with diverse bioactivities. In this study, a novel fucose-specific lectin (MEP5) was isolated from M. esculenta, with a molecular weight of 33.12 kDa and a characteristic carbohydrate-recognition domain. Structural analysis revealed that MEP5 predominantly consists of random coils and extended strands, with α-helix as a minor component. In a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) mouse model, MEP5 treatment significantly ameliorated NAFLD by normalizing lipid profiles (TG, TC, LDL-C, HDLC), repairing adipose tissue morphology, and reducing hepatic lipid accumulation. Mechanistically, MEP5 exerted hepatoprotective effects through transcriptional modulation of key lipid metabolic regulators (PPARα, SREBP-1, Fasn, Hmgcr, G6pc1, UCP-1, CD36, ABCA1, PRDM16). Network pharmacology and experimental validation indicated that MEP5 alleviated hepatic steatosis by inhibiting the MAPK signaling pathway. Additionally, integrated metabolomic and 16S rRNA sequencing analyses identified alterations in the gut microbiome, with enrichment of Duncaniella, CAG-485, and UBA3282, and depletion of Desulfovibrio-R, which were linked to MEP5's protective effects. This study highlights the potential of M. esculenta lectins as a therapeutic tool, advancing our understanding of gut-liver interactions and metabolic regulation.