Nootkatone suppresses TLR4/NF-κB/NLRP3 pathway to alleviate non-alcoholic fatty liver disease via modulating gut microbiota  

作　　者：Rongrong Fu Wenqing Xue Jingjie Liang Lechen Wang Min Zhang Jing Meng 

机构地区：[1]State Key Laboratory of Food Nutrition and Safety,College of Food Science and Engineering,Tianjin University of Science and Technology,Tianjin 300457,China [2]China-Russia Agricultural Processing Joint Laboratory,Tianjin Agricultural University,Tianjin 300384,China [3]Tianjin International Joint Academy of Biomedicine,Tianjin 300457,China

出　　处：《Food Science and Human Wellness》2025年第4期1398-1410,共13页食品科学与人类健康(英文)

基　　金：supported by grants from National Natural Science Foundation of China(82072709,81902441);Natural Science Foundation of Tianjin Municipal(23JCYBJC00850);China Postdoctoral Science Foundation(2022M712374);Tianjin“131”Innovative Talent Team Project(201926)。

摘　　要：Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide.Gut microbiota and its metabolites alteration are closely related to NAFLD.Nootkatone is an edible flavorant derived from grapefruit which has a variety of biological activities.However,the precise mechanisms of nootkatone on NAFLD remains to be defined.Our results showed that nootkatone prevented body weight gain and decreased serum lipid level,hepatic lipogenesis,hepatic proinflammatory cytokines secretion in NAFLD mice.Also,nootkatone attenuated inflammatory response via inhibiting TLR4/NF-κB/NLRP3 pathway.Moreover,nootkatone restored intestinal barrier damage through increasing tight junction proteins and short chain fatty acids contents.Further 16S rRNA sequencing of colonic content suggested that nootkatone recovered the disturbed gut microbiota to improve NAFLD.Spearman correlation analysis between gut microbiota and NAFLD related parameters indicated that nootkatone regulated lipid metabolism and immunity via altering the gut microbiota.In conclusion,these findings revealed that nootkatone alleviated hepatic lipid homeostasis and inflammatory response in NAFLD mice,which associated with intestinal barrier integrity and the regulation of gut microbiota.This study provides new perspectives that nootkatone has efficacy on NAFLD via“gut-liver axis”,and nootkatone is expected to be developed as a functional food additive.

关 键 词：Nootkatone Non-alcoholic fatty liver disease Hepatic inflammation TLR4/NF-κB/NLRP3 Gut microbiome 

分 类 号：R57[医药卫生—消化系统]