Anti-toll-like receptor 2 antibody ameliorates hepatic injury, inflammation, fibrosis and steatosis in obesity-related metabolic disorder rats via regulating MAPK and NF-κB pathways

Wu, Linquan; Sun, Jianjun; Liu, Li; Du, Xiaohong; Liu, Yan; Yan, Xiaofei; Osoro, Ezra Kombo; Zhang, Fujun; Feng, Lin; Dong, Liang; Li, Yazhao; Qian, Chen; Sun, Sha; Zhang, Lei; Lan, Xi; Li, Dongmin; Lu, Shemin

doi:10.1016/j.intimp.2020.106368

Cited by 21 publications

(15 citation statements)

References 64 publications

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“…Following the formation of excess lipid accumulation in the liver, lipid peroxidation is induced, and the oxidative stress process begins. Then, the production and release of pro-inflammatory cytokines, such as TNF-α and IL-6, further induce liver inflammation and exacerbate the progression of NAFLD to NASH [ 43 ]. We observed that CPP supplementation significantly reduced the increase in pro-inflammatory cytokines, such as TNF-α, IL-6, and MCP-1, caused by HFD.…”

Section: Discussionmentioning

confidence: 99%

The Regulatory Effects of Citrus Peel Powder on Liver Metabolites and Gut Flora in Mice with Non-Alcoholic Fatty Liver Disease (NAFLD)

Zhang

Ruan

et al. 2021

Foods

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Gannan navel orange and Jinggang pomelo, belonging to the genus Citrus, are good sources of phenolic compounds, which are mainly concentrated in the peel. These phenolic compounds are considered promising in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). In order to maximize nutrients retention and bioactivity in the peel, pomelo peel and orange peel were processed using freeze-drying technology and mixed in the ratio (pomelo peel powder 50% and orange peel powder 50%) to make citrus peel powder (CPP). The purpose of this study was to explore new strategies and mechanisms associated with the consumption of CPP to alleviate nonalcoholic fatty liver injury, lipid metabolism disorders, and gut microbiota dysbiosis in obese mice induced by high-fat diet (HFD). The results showed that after 12 weeks of CPP administration, CPP supplementation had a strong inhibitory effect on HFD-induced weight gain, hepatic fat accumulation, dyslipidemia, and the release of pro-inflammatory cytokines. In particular, CPP modulates the composition of the intestinal flora, such as increasing the relative abundance of phylum Firmicutes, genus Faecalibaculum, genus Lactobacillus, genus Dubosiella, and genus Lachnospiraceae_NK4A136_ group and decreasing the relative abundance of phylum Bacteroidota, genus Helicobacter, and genus Bacteroides. These results suggest that CPP has a preventive effect on NAFLD, which can be related to the regulation of intestinal flora.

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Section: Discussionmentioning

confidence: 99%

The Regulatory Effects of Citrus Peel Powder on Liver Metabolites and Gut Flora in Mice with Non-Alcoholic Fatty Liver Disease (NAFLD)

Zhang

Ruan

et al. 2021

Foods

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“…72 TNF-α can activate downstream NF-κB and MAPKs family proteins, which induces the organism inflammation. 73 It has been shown that prebiotics can reduce low-grade intestinal inflammation by regulating the disordered gut microbiota. 74,75 In this study, the EN formulas intervention reduced the levels of pro- inflammatory cytokine (i e TNF-α).…”

Section: Discussionmentioning

confidence: 99%

Nutritional Effects of the Enteral Nutritional Formula on Regulation of Gut Microbiota and Metabolic Level in Type 2 Diabetes Mellitus Mice

Wei¹,

Jia²,

Xue³

et al. 2021

DMSO

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Purpose Due to the adverse effects of antidiabetic drugs, nowadays, nutraceuticals have been of much interest to investigators. Therefore, the present study aimed to explore the potential effects of enteral nutritional (EN) formulas on the gut microbiota and metabolic regulation of type 2 diabetes mellitus (T2DM) mice and compare the differences between whey protein and soy protein. Methods EN formulas made of whey protein or soy protein were administered for five weeks and then mice tissue samples were obtained to examine the metabolic parameters and histopathology of the pancreas, liver, jejunum and colon. 16S rRNA V3-V4 region gene sequencing was used to analyze the changes in the gut microbiota. Results After the five-week intervention, the alpha diversity had recovered slightly, and the soy protein group (SPG) achieved a better effect than the whey protein group (LPG). The overall composition of gut microbiota was regulated. The abundance of Bacteroidetes and TM7 had raised significantly and the abundance of Firmicutes and Deferribacteres had declined after treatment, with no significant difference between the LPG and SPG. The types of beneficial bacteria were increased at the genus and species level. The level of hexokinase (HK) and pyruvate kinase (PK) had significantly recovered and inhibited the level of α-glucosidase. In addition, the EN formulas treatment reduced the levels of inflammatory factor (TNF-α) in liver and muscle. The level of glucose transporter type 2 (GLUT-2) levels in the liver and intestine also significantly increased. Moreover, the metabolism regulation of the SPG was better than that of the LPG. The EN formulas treatment improved the pancreas, liver, jejunum and colon histology. Conclusion The EN formulas regulated the overall structure of the gut microbiota and improved the metabolic level in streptozotocin/high-fat diet (STZ/HFD) diabetic mice. Therefore, EN formula may potentially become an effective nutritional adjunctive therapy for T2DM.

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“…Abnormal activation of Toll-like receptors (TLRs) had been found to cause obesity-related systemic inflammation and associated comorbidities in obese rats [ 41 ]. Inhibition of TLRs could reduce the activation of MAPKs and NF-κB and ameliorate obesity-induced NAFLD [ 42 ]. CXCR4 was a G protein-coupled chemokine receptor and plays a key role in improving NAFLD after BS [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

A novel immune-related genes signature after bariatric surgery is histologically associated with non-alcoholic fatty liver disease

et al. 2021

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Increasing evidence shows that immune-related genes (IRGs) play an important role in bariatric surgery (BS). We identified differentially expressed immune-related genes (DEIRGs) of adipose tissue after BS by analysing the two expression profiles of GEO (GSE59034 and GSE29409). Subsequently, enrichment analysis, GSEA and PPI networks were examined to identify the hub IRGs and related pathways. The performance of the signature was evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC). CIBERSORT algorithm was used to evaluate the relative abundance of infiltrated immune cells.42 DEIRGs were found between the GSE59034 and GSE29409 datasets. The AUC of the signature was 0.904 and 0.865 in the GSE58979 and GSE48452, respectively. Interestingly, the signature also showed good performance in diagnosing non-alcoholic fatty liver disease (NAFLD) (AUC was 0.834 and 0.800, respectively). The number of neutrophils, macrophages M2, macrophages M0 and dendritic cells activated decreased significantly. After BS, the infiltration of T cells regulatory, monocytes, mast cells resting and plasma cells in adipose tissue increased. The novel proposed IRGs signature reveals the underlying immune mechanism of BS and is a promising biomarker for distinguishing the severity of NAFLD. This will provide new insights into strategies for treating obesity and NAFLD.

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Anti-toll-like receptor 2 antibody ameliorates hepatic injury, inflammation, fibrosis and steatosis in obesity-related metabolic disorder rats via regulating MAPK and NF-κB pathways

Cited by 21 publications

References 64 publications

The Regulatory Effects of Citrus Peel Powder on Liver Metabolites and Gut Flora in Mice with Non-Alcoholic Fatty Liver Disease (NAFLD)

The Regulatory Effects of Citrus Peel Powder on Liver Metabolites and Gut Flora in Mice with Non-Alcoholic Fatty Liver Disease (NAFLD)

Nutritional Effects of the Enteral Nutritional Formula on Regulation of Gut Microbiota and Metabolic Level in Type 2 Diabetes Mellitus Mice

A novel immune-related genes signature after bariatric surgery is histologically associated with non-alcoholic fatty liver disease

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