Abstract
High-fat diet (HFD) and overnutrition are important starting factors that may alter intestinal microbiota, lipid metabolism, and systemic inflammation. However, there were few studies on how intestinal microbiota contributes to tissue steatosis and hyperlipidemia. Here, we investigated the effect of lipid metabolism disorder–induced inflammation via toll-like receptor 2 (TLR-2), toll-like receptor 4 (TLR-4), and nuclear factor-κB (NF-κB) pathways at the intestinal level in response to HFD. Twenty 80-day-old male New Zealand White rabbits were randomly divided into the normal diet group (NDG) and the high-fat diet group (HDG) for 80 days. Growth performance, blood biochemical parameters, lipid metabolism, inflammation, degree of tissue steatosis, and intestinal microbial composition were measured. HFD increased the relative abundance of Christensenellaceae_R_7_group, Marvinbryantia, Akkermansia etc., with a reduced relative abundance of Enterorhabdus and Lactobacillus. Moreover, HFD caused steatosis in the liver and abdominal fat and abnormal expression of some genes related to lipid metabolism and tight junction proteins. The TLR-2, TLR-4, NF-κB, TNF-α, and IL-6 were confirmed by overexpression with downregulation of IL-10. Serum biochemical indices (TG, TCHO, LDL-C, and HDL-C) were also increased, indicating evidence for the development of the hyperlipidemia model. Correlation analysis showed that this microbial dysbiosis was correlated with lipid metabolism and inflammation, which were associated with the intestinal tract’s barrier function and hyperlipidemia. These results provide an insight into the relationship between HFD, the intestinal microbiota, intestinal barrier, tissue inflammation, lipid metabolism, and hyperlipidemia.
Key points
• High-fat diet leads to ileal microbiota disorders
• Ileal microbiota mediates local and systemic lipid metabolism disorders and inflammation
• There is a specific link between ileal microbiota, histopathology, and hyperlipidemia
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Data availability
The authors declare that data supporting the findings of this study are available within the article.
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Acknowledgements
Special thanks to the Key Laboratory of Innovation and Utilization of Grassland Resources in Henan Province to provide technical support.
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Financial support of Science and Technology Innovation Team of Henan Province High Quality Forage and Animal Health (No.22IRTSTHN022), the earmarked fund for CARS (CARS-34).
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B.L., Z.W., and X.Z. performed the experiments and analyzed the data. Z.G., X.D., and M.A. participated in the data collection. Y.C., M.Z.G., and D.L. assisted with the animal experimentation. Z.G. and Q.A. wrote the manuscript draft. Y.S. supervised the study. All the authors have read and agreed to the published version of the manuscript.
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Guo, Z., Ali, Q., Abaidullah, M. et al. High fat diet–induced hyperlipidemia and tissue steatosis in rabbits through modulating ileal microbiota. Appl Microbiol Biotechnol 106, 7187–7207 (2022). https://doi.org/10.1007/s00253-022-12203-7
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DOI: https://doi.org/10.1007/s00253-022-12203-7