Licochalcone A alleviates MAFLD in mice by activating AMPK signaling through regulation of O-GlcNAcylation, in a manner dependent on gut microbiota remodeling and the associated metabolite dodecanedioic acid.
Licochalcone A (LA) alleviated hepatic lipid accumulation, oxidative stress, and inflammation in MAFLD mice.
LA activated the AMPK pathway in MAFLD mice through regulation of O-GlcNAcylation.
LA restored intestinal barrier function and reshaped the gut microbiota, increasing the relative abundance of Muribaculaceae and Parasutterella.
Gut microbiota are indispensable for LA-mediated MAFLD amelioration and for hepatic O-GlcNAcylation regulation.
Dodecanedioic acid (DA), a lipid-metabolism-related metabolite, improved MAFLD through AMPK activation.
This study looked at licochalcone A, a compound from licorice, as a possible way to protect against metabolic-associated fatty liver disease (MAFLD), a common chronic liver condition. In mice with MAFLD, the compound reduced fat buildup in the liver, oxidative stress, and inflammation. The researchers traced how this happens. Licochalcone A appeared to switch on AMPK, a key cellular energy and fat-metabolism regulator, by changing a chemical modification on proteins called O-GlcNAcylation. It also improved the gut barrier and shifted gut bacteria, increasing groups such as Muribaculaceae and Parasutterella. Experiments that wiped out gut bacteria or transferred them between animals indicated that the gut microbes were needed for the liver benefits. A metabolite linked to this process, dodecanedioic acid, also helped through AMPK in mice and in cell experiments. This research suggests that part of licochalcone A's liver benefit works through a gut-liver connection. The findings come from mice and cell models, so they do not show that the compound would work in people, and the abstract gives no dosing details.
Wang S, Guo S, Wang X, Wang H, Wang J, Ma Y, et al.. (2026). Licochalcone A Ameliorates Metabolic-Associated Fatty Liver Disease by AMPK Signaling Pathway Activation through O-GlcNAcylation Regulation and Remodeling of Gut Microbiota and Associated Metabolites.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c04497