Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells

Yao, Jinmei; Ying, Hua‐Zhong; Zhang, Huan‐Huan; Qiu, Fen-Sheng; Wu, Junqi; Yu, Chunjing

doi:10.1016/j.freeradbiomed.2022.12.085

Cited by 17 publications

(12 citation statements)

References 65 publications

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“…As NAFLD and obesity progress, macrophages accumulate in the liver and adipose tissue and continuously release pro-inflammatory factors such as TNF-α, ultimately leading to mild chronic inflammation [ 51 ]. Studies have shown that TNF-α is involved in inhibiting the uptake of free fatty acids and the activity of lipid metabolism-related enzymes, promoting fat synthesis and mediating the production of adipokines [ 52 ]. Additionally, studies have shown that the TNF is a key adipokine that regulates downstream pro-inflammatory cytokines such as IL-6 and monocyte chemoattractant protein-1, further exacerbating adipose tissue inflammation and even insulin resistance [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

In silico and in vivo demonstration of the regulatory mechanism of Qi-Ge decoction in treating NAFLD

Peng

et al. 2023

Annals of Medicine

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Background Nonalcoholic fatty liver disease (NAFLD), a chronic and progressive liver disease, often causes steatosis and steatohepatitis. Qi-Ge decoction (QGD) shows a good effect against NAFLD in the clinic. But the molecular mechanism for QGD in improving NAFLD is unknown. Purpose This study explored the molecular mechanism of QGD in NAFLD model rats using comprehensive network pharmacology, molecular docking and in vivo verification strategies. Methods Active components and targets of QGD were obtained from public database. The overlapped genes between QGD and NAFLD targets were analyzed by enrichment analysis. Active components and targets were used to predict molecular docking analysis. Finally, seven key targets were screened out and the gene expression were verified in the NAFLD rat’s liver tissues after QGD treatment. Results Fifty-eight common QGD therapeutic targets were associated with NAFLD. Molecular docking demonstrated that seven targets had strong binding ability for the corresponding active ingredients. GO analysis identified 18 biological process entries, which were mainly related to regulation of lipid storage, lipid localization and peptide transport. KEGG analysis identified multiple signaling pathways, which were mainly associated with tumor necrosis factor signaling and NAFLD. In vivo data confirmed that the effect of QGD in the treatment of NAFLD was mainly exerted through improving liver steatosis and inflammatory cell infiltration. Additionally, QGD upregulated the expression of MAPK8 and ESR1 and downregulated the transcriptional expression of IL6, VEGFA, CASP3, EGFR and MYC. These targets may affect lipid metabolism by regulating lipid storage and inflammation. Conclusion The integration of results obtained in silico and in vivo indicated that QGD regulates multiple targets, biological processes and signaling pathways in NAFLD, which may represent a complex molecular mechanism by which QGD improves NAFLD. Key messages QGD intervention is related to multiple biological processes such as inflammation, oxidation and cell apoptosis in NAFLD. Lipid and atherosclerosis, TNF signaling pathway, IL-17 signaling pathway, non-alcoholic fatty liver disease and AGE-RAGE signaling pathway in diabetic complications are the main pathways for QGD intervention NAFLD. The active components of QGD can form good binding with relevant target proteins through intermolecular forces, exhibiting excellent docking activity.

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Section: Discussionmentioning

confidence: 99%

In silico and in vivo demonstration of the regulatory mechanism of Qi-Ge decoction in treating NAFLD

Peng

et al. 2023

Annals of Medicine

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“…Higher hepatic RBP4 levels are correlated with pathohistological features of NASH patients [ 149 ]. Its transcription is stimulated by activated STAT3 in hepatocytes upon exposure to TNFα [ 150 ]. RBP4 promotes M1 polarization of hepatic Kupffer cells via activation of NOX2/NF-κB/TNFα pathway.…”

Section: The Secreted Proteins-receptor Signaling Regulates Nash Prog...mentioning

confidence: 99%

Drug targets regulate systemic metabolism and provide new horizons to treat nonalcoholic steatohepatitis

Wang,

Yu,

Cen

et al. 2024

Metabolism Open

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“…Another study by Jin-Mei Yao et al has focused on retinol-binding protein 4 (rRBP4), revealing that rRBP4 treatment increases intracellular ROS levels and promotes the expression of M1-like macrophage markers, such as iNOS, TNF-α, and IL-1β, while reducing the expression of M2-like macrophage markers, such as IL-10, Arg-1, and YM1. This induces KC polarization to the M1 type, and the process is closely related to the NOX2/NF-κB pathway ( Yao et al, 2023 ).…”

Section: Activation Of Kcsmentioning

confidence: 99%

Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions

Wei

Zhao

et al. 2023

Front. Cell Dev. Biol.

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Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of liver disease worldwide. These conditions can lead to cirrhosis, liver cancer, liver failure, and other related ailments. At present, liver transplantation remains the sole treatment option for end-stage NASH, leading to a rapidly growing socioeconomic burden. Kupffer cells (KCs) are a dominant population of macrophages that reside in the liver, playing a crucial role in innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, and triggering immune responses. Moreover, they interact with other liver cells during the pathogenesis of NAFLD, and this crosstalk may either delay or exacerbate disease progression. Stimulation by endogenous signals triggers the activation of KCs, resulting in the expression of various inflammatory factors and chemokines, such as NLRP3, TNF-α, IL-1B, and IL-6, and contributing to the inflammatory cascade. In the past 5 years, significant advances have been made in understanding the biological properties and immune functions of KCs in NAFLD, including their interactions with tissue molecules, underlying molecular mechanisms, signaling pathways, and relevant therapeutic interventions. Having a comprehensive understanding of these mechanisms and characteristics can have enormous potential in guiding future strategies for the prevention and treatment of NAFLD.

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Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells

Cited by 17 publications

References 65 publications

In silico and in vivo demonstration of the regulatory mechanism of Qi-Ge decoction in treating NAFLD

In silico and in vivo demonstration of the regulatory mechanism of Qi-Ge decoction in treating NAFLD

Drug targets regulate systemic metabolism and provide new horizons to treat nonalcoholic steatohepatitis

Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions

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