Periodontal pathogen Fusobacterium nucleatum infection accelerates hepatic steatosis in high‐fat diet‐fed ApoE knockout mice by inhibiting Nrf2/Keap1 signaling

Author:

Wu Peiyao12ORCID,Bie Mengyao12,Zhou Jieyu12,Wang Jun12ORCID,Zhao Lei12

Affiliation:

1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University Chengdu China

2. Department of Periodontics, West China School & Hospital of Stomatology Sichuan University Chengdu China

Abstract

AbstractAimsThis study sought to explore the impact of Fusobacterium nucleatum on hepatic steatosis in apolipoprotein E (ApoE) knockout (KO) mice induced by a high‐fat diet (HFD) and elucidate the underlying mechanism.MethodsApoE KO mice, on a HFD, received F. nucleatum oral inoculation every other day. After 24 weeks, body weight, liver weight, and liver index were assessed. Serum biochemistry and pro‐inflammatory factors in serum and liver were analyzed. The histopathology of right maxilla and live were performed. Oil red O, immunohistochemistry, and immunofluorescence staining for the liver were conducted. Myeloperoxidase (MPO) activity, apoptosis, lipid reactive oxygen species (ROS), ROS, lipid peroxides, and hepatic lipids were also evaluated. Liver inflammation, fibrosis, de novo lipogenesis (DNL)‐related molecule, and Nrf2/Keap1‐related signaling molecule gene/protein expression were determined by real‐time PCR (RT‐PCR) and/or Western blot (WB) analysis.ResultsHFD‐fed ApoE KO mice infected by F. nucleatum demonstrated significant changes, including increased body and liver weight, elevated proinflammatory factors and lipids in serum and liver, as well as neutrophil infiltration, fibrosis, apoptosis, oxidative stress, and lipid peroxidation in the liver. Additionally, F. nucleatum stimulates hepatic lipid accumulation and activates de novo lipogenesis (DNL), while simultaneously suppressing the Nrf2/Keap1 antioxidant pathway.ConclusionIn conclusion, our study reveals that oral inoculation of F. nucleatum might promote hepatic steatosis by inhibiting Nrf2/Keap1 pathway.

Funder

National Key Research and Development Program of China

Sichuan Province Science and Technology Support Program

Publisher

Wiley

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