Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol.
Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol.
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西方饮食通过重塑肠道微生物区系和增加2-油酰甘油的产生，促进了雄性小鼠非酒精性脂肪性肝炎的发病。
DOI：
10.1038/s41467-023-35861-1
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发表时间：
2023-01-16
影响因子：
16.6
通讯作者：
Li, Guangfu
中科院分区：
文献类型：
--
作者：
Yang, Ming;Qi, Xiaoqiang;Li, Nan;Kaifi, Jussuf T.;Chen, Shiyou;Wheeler, Andrew A.;Kimchi, Eric T.;Ericsson, Aaron C.;Scott Rector, R.;Staveley-O'Carroll, Kevin F.;Li, Guangfu
西方饮食和肠道微生物群之间的相互作用推动了非酒精性脂肪性肝病的发展及其向非酒精性脂肪性肝炎的进展。然而，导致非酒精性脂肪性肝炎的特定微生物和代谢介质仍有待确定。在这里，胆碱低、高脂肪、高糖饮食，代表了典型的西方饮食，被称为CL-HFS，成功地诱导了雄性小鼠非酒精性脂肪性肝炎，并具有人类疾病的一些特征，如肝脏炎症、脂肪变性和纤维化。元分类学和代谢组学研究发现，产蓝藻和2-油基甘油是导致cl - hfs诱导的非酒精性脂肪性肝炎的临床相关细菌和代谢介质。体内研究证实，在正常饮食或cl - hfs喂养的小鼠中，蓝藻产品和2-油基甘油均可促进肝脏炎症和肝纤维化。细胞和分子研究表明，GPR119/TAK1/NF-κB/TGF-β1信号通路介导2-油基甘油诱导的巨噬细胞启动和随后的肝星状细胞活化。这些发现促进了我们对非酒精性脂肪性肝炎发病机制的理解，并为开发基于微生物组/代谢物的非酒精性脂肪性肝炎治疗策略提供了靶点。据报道，西方饮食和肠道微生物群的相互作用与非酒精性脂肪性肝炎（NASH）的发展有关。本文作者报道了蓝藻产品和2-油基甘油是促进雄性小鼠肝脏炎症和肝纤维化的细菌和代谢介质。
The interplay between western diet and gut microbiota drives the development of non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. However, the specific microbial and metabolic mediators contributing to non-alcoholic steatohepatitis remain to be identified. Here, a choline-low high-fat and high-sugar diet, representing a typical western diet, named CL-HFS, successfully induces male mouse non-alcoholic steatohepatitis with some features of the human disease, such as hepatic inflammation, steatosis, and fibrosis. Metataxonomic and metabolomic studies identify Blautia producta and 2-oleoylglycerol as clinically relevant bacterial and metabolic mediators contributing to CL-HFS-induced non-alcoholic steatohepatitis. In vivo studies validate that both Blautia producta and 2-oleoylglycerol promote liver inflammation and hepatic fibrosis in normal diet- or CL-HFS-fed mice. Cellular and molecular studies reveal that the GPR119/TAK1/NF-κB/TGF-β1 signaling pathway mediates 2-oleoylglycerol-induced macrophage priming and subsequent hepatic stellate cell activation. These findings advance our understanding of non-alcoholic steatohepatitis pathogenesis and provide targets for developing microbiome/metabolite-based therapeutic strategies against non-alcoholic steatohepatitis. Interplay of western diet and gut microbiota has been reported to be involved in the development of nonalcoholic steatohepatitis (NASH). Here the authors report that Blautia producta and 2-oleoylglycerol are bacterial and metabolic mediators that promote liver inflammation and hepatic fibrosis in male mice.
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