2. Academic Validation
  3. 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

  • Nat Commun. 2023 Jan 16;14(1):228. doi: 10.1038/s41467-023-35861-1.
Ming Yang # 1,  Xiaoqiang Qi # 1,  Nan Li # 1 2,  Jussuf T Kaifi 1 3 4,  Shiyou Chen 1,  Andrew A Wheeler 1,  Eric T Kimchi 1 3 4,  Aaron C Ericsson 5,  R Scott Rector 6 7,  Kevin F Staveley-O'Carroll 8 9 10,  Guangfu Li 11 12 13 14
Affiliations

Affiliations

  • 1 Department of Surgery, University of Missouri, Columbia, MO, 65212, USA.
  • 2 Department of Radiation Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, 110001, China.
  • 3 Ellis Fischel Cancer Center, University of Missouri, Columbia, MO, 65212, USA.
  • 4 Harry S. Truman Memorial VA Hospital, Columbia, MO, 65201, USA.
  • 5 Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65212, USA.
  • 6 Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, 65212, USA.
  • 7 Department of Medicine-Gastroenterology and Hepatology, University of Missouri, Columbia, MO, 65212, USA.
  • 8 Department of Surgery, University of Missouri, Columbia, MO, 65212, USA. ocarrollk@health.missouri.edu.
  • 9 Ellis Fischel Cancer Center, University of Missouri, Columbia, MO, 65212, USA. ocarrollk@health.missouri.edu.
  • 10 Harry S. Truman Memorial VA Hospital, Columbia, MO, 65201, USA. ocarrollk@health.missouri.edu.
  • 11 Department of Surgery, University of Missouri, Columbia, MO, 65212, USA. liguan@health.missouri.edu.
  • 12 Ellis Fischel Cancer Center, University of Missouri, Columbia, MO, 65212, USA. liguan@health.missouri.edu.
  • 13 Harry S. Truman Memorial VA Hospital, Columbia, MO, 65201, USA. liguan@health.missouri.edu.
  • 14 Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, 65212, USA. liguan@health.missouri.edu.
  • # Contributed equally.
PMID: 36646715 DOI: 10.1038/s41467-023-35861-1
Abstract

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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z