Toll-like receptor 3 ablation prevented high-fat diet-induced obesity and metabolic disorder

Zhang, Guoqing; Ran, Li; Li, Wu; Yang, Sijia; Sun, Qing; Yin, Hongping; Wang, Cui; Hou, Biyu; Wang, Huanhuan; Yu, Liping; Chen, Rucheng; Shi, Liyun; Zhang, Kezhong; Liew, Chong Wee; Qiang, Guifen; Sun, Qinghua; Liu, Cuiqing

doi:10.1016/j.jnutbio.2021.108761

Cited by 12 publications

(8 citation statements)

References 37 publications

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“…Signaling pathways include GPCR ligand binding [89], neutrophil degranulation [90], immune system [91], metabolism of lipids [92] and signal transduction [93] made great contribution to the development of IPF. MAP3K15 [94], PRTN3 [95], CX3CR1 [96], AGRP (agouti related neuropeptide) [97], MPO (myeloperoxidase) [98], CD5L [99], S100A8 [100], NPR3 [101], VEGFD (vascular endothelial growth factor D) [102], CXCL11 [103], IL1A [104], CBS (cystathionine beta-synthase) [105], WNT7A [106], SCD (stearoyl-CoA desaturase) [107], LRP2 [108], SLC6A4 [109], BDNF (brain derived neurotrophic factor) [110], CXCL10 [111], ANGPTL7 [112], S100A9 [113], NPY1R [114], IL1B [115], GPIHBP1 [116], CYP1B1 [117], CD36 [118], MACROD2 [119], TRIB3 [120], SPX (spexin hormone) [121], PCSK9 [122], GPD1 [123], CDH13 [124], FFAR4 [125], FGF2 [126], FASN (fatty acid synthase) [127], DGAT2 [128], DACH1 [129], PNPLA3 [130], FGF9 [131], SLC7A11 [132], CLIC5 [133], VIP (vasoactive intestinal peptide) [134], SMAD6 [135], BMPR2 [136], APOA1 [137], INSIG1 [138], TLR3 [139], NLRP12 [140], ADRB1 [141], TLR8 [142], GATA3 [143], CCR2 [144], TLR7 [145], CCRL2 [146], BMPER (BMP binding endothelial regulator) [147], CAV1 [148], TFPI (tissue factor pathway inhibitor) [149], FADS1 [150], SUCNR1 [151], CADM2 [152], SLC19A3 [153], SGCG (sarcoglycan gamma) [154], ADH1B [155], NEGR1 [156], HSD17B12 [157], OXTR (oxytocin receptor) [158] and ANKK1 […”

Section: Discussionmentioning

confidence: 99%

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analysis of DEGs were performed. Then, a protein protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst database was used to construct the targeted microRNAs (miRNAs) and transcription factors (TFs) of the hub genes. Finally receiver operating characteristic (ROC) curve analysis was used to validates the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8 and EFHC2 were selected. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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Section: Discussionmentioning

confidence: 99%

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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“…Here, we demonstrated that mice harboring an overexpression of HSP60 presented suppressed mt-dsRNA abundance, as well as reduced body weight and adipose tissue of various parts, in line with the notion of suppressed TLR3/MDA5/p-IRF3 signaling pathways and pro-inflammatory cytokines expression. Recently, one study showed that TLR3 ablation prevented obesity and metabolic disorders [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Protein 60 Restricts Release of Mitochondrial dsRNA to Suppress Hepatic Inflammation and Ameliorate Non-Alcoholic Fatty Liver Disease in Mice

Huang

Wang

et al. 2022

IJMS

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Non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, consists of fat deposited (steatosis) in the liver due to causes besides excessive alcohol use. The folding activity of heat shock protein 60 (HSP60) has been shown to protect mitochondria from proteotoxicity under various types of stress. In this study, we investigated whether HSP60 could ameliorate experimental high-fat diet (HFD)-induced obesity and hepatitis and explored the potential mechanism in mice. The results uncovered that HSP60 gain not only alleviated HFD-induced body weight gain, fat accumulation, and hepatocellular steatosis, but also glucose tolerance and insulin resistance according to intraperitoneal glucose tolerance testing and insulin tolerance testing in HSP60 transgenic (HSP60Tg) compared to wild-type (WT) mice by HFD. Furthermore, overexpression of HSP60 in the HFD group resulted in inhibited release of mitochondrial dsRNA (mt-dsRNA) compared to WT mice. In addition, overexpression of HSP60 also inhibited the activation of toll-like receptor 3 (TLR3), melanoma differentiation-associated gene 5 (MDA5), and phosphorylated-interferon regulatory factor 3 (p-IRF3), as well as inflammatory biomarkers such as mRNA of il-1β and il-6 expression in the liver in response to HFD. The in vitro study also confirmed that the addition of HSP-60 mimics in HepG2 cells led to upregulated expression level of HSP60 and restricted release of mt-dsRNA, as well as downregulated expression levels of TLR3, MDA5, and pIRF3. This study provides novel insight into a hepatoprotective effect, whereby HSP60 inhibits the release of dsRNA to repress the TLR3/MDA5/pIRF3 pathway in the context of NAFLD or hepatic inflammation. Therefore, HSP60 may serve as a possible therapeutic target for improving NAFLD.

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“…Therefore, the level of IL-33 would be higher in the HFD group, and IL-33 would have expanded Tregs through the IL-33/ST2 signaling pathway. Furthermore, a HFD could activate cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling, nuclear factor kappa-B (NF-κB) signaling ( 28 , 29 ), and Toll-like receptors (TLRs) (2/3/4) signaling ( 30 ). cGAS, as the primary cytosolic DNA sensor, recognizes various pathogen-associated molecular patterns to initiate and enhance inflammation ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Twelve-week high-fat diet for improving adverse ventricular remodeling post-myocardial infarction by alleviating local inflammation

Yang¹,

Mai²,

Su³

et al. 2022

Ann Transl Med

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Background: Many studies have examined how to achieve better outcomes in myocardial infarction (MI) patients with mild obesity or who are overweight. However, the influence of a high-fat diet (HFD) and the underlying mechanisms by which it can affect ventricular remodeling following MI are poorly understood.This study investigated the impact of a 12-week HFD on the left ventricular (LV) remodeling of permanent MI models and immune cell involvement.Methods: Male C57BL/6J mice were fed HFD or normal diet (ND). After 8 weeks of feeding, mice underwent cardiac left anterior descending coronary artery ligation, and the same diet was continued for a further 4 weeks. Cardiac structure and function were detected using echocardiography. Cardiac fibrosis was evaluated using histological staining at 7 and 28 days post-MI. Infiltration of various immune cells was examined using flow cytometry and immunofluorescence at 7 days post-MI.Results: Compared with a ND, the 12-week HFD feeding significantly alleviated ventricular remodeling following MI. HFD mice showed reduced infiltration of neutrophils, a higher proportion of M2/M1 macrophages, decreased conventional and monocyte-derived dendritic cells (moDCs) in the injured myocardium, and elevated levels of regulatory T cells (Tregs). Further investigation of dendritic cells (DCs) phenotypes indicated downregulated expression of major histocompatibility complex class II (MHCII). It also showed costimulatory molecules CD40 and CD86 on conventional and moDCs in mediastinal lymph nodes (mLNs).Conclusions: This study demonstrated the protective effect of a 12-week HFD on ventricular remodeling following MI via the alleviation of local inflammation.

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Toll-like receptor 3 ablation prevented high-fat diet-induced obesity and metabolic disorder

Cited by 12 publications

References 37 publications

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Heat Shock Protein 60 Restricts Release of Mitochondrial dsRNA to Suppress Hepatic Inflammation and Ameliorate Non-Alcoholic Fatty Liver Disease in Mice

Twelve-week high-fat diet for improving adverse ventricular remodeling post-myocardial infarction by alleviating local inflammation

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