Altered bile acid composition and disposition in a mouse model of non-alcoholic steatohepatitis

Suga, Toshio; Yamaguchi, Hiroaki; Ogura, Jiro; Shoji, Saori; Maekawa, Masamitsu; Mano, Nariyasu

doi:10.1016/j.taap.2019.114664

Cited by 54 publications

(48 citation statements)

References 47 publications

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“…Moreover, accumulation of lipid droplets and collagen fibres were confirmed by H&E and MT staining, respectively, in the WT-CDAHFD and KO-CDAHFD groups. These observations are consistent with those in previous studies (6,8). Suga et al observed that mice fed with CDAHFD for 6 weeks show hepatic steatosis and fibrosis (8).…”

Section: Discussionsupporting

confidence: 93%

“…In addition, these inflammatory cytokines are regulated by nuclear factor-κB (NF-κB). Furthermore, the progression of liver fibrosis in NASH is associated with alterations in the extracellular matrix mainly by increased production of type I collagen (5)(6)(7)(8)(9). NASH progresses with increasing degrees of fibrosis, with the most common complication being cirrhosis (2).…”

Section: Introductionmentioning

confidence: 99%

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Effects of renalase deficiency on liver fibrosis markers in a nonalcoholic steatohepatitis mouse model

et al. 2021

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Progression of nonalcoholic steatohepatitis (NASH) is attributed to several factors, including inflammation and oxidative stress. In recent years, renalase has been reported to suppress oxidative stress, apoptosis and inflammation. A number of studies have suggested that renalase may be associated with protecting the liver from injury. The present study aimed to clarify the effects of renalase knockout (KO) in mice with NASH that were induced with a choline-deficient high-fat diet (CDAHFD) supplemented with 0.1% methionine. Wild type (WT) and KO mice (6-week-old) were fed a normal diet (ND) or CDAHFD for 6 weeks, followed by analysis of the blood liver function markers and liver tissues. CDAHFD intake was revealed to increase blood hepatic function markers, lipid accumulation and oxidative stress compared with ND, but no significant differences were observed between the WT and KO mice. However, in the KO-CDAHFD group, the Adgre1 and Tgfb1 mRNA levels were significantly higher, and α-SMA expression was significantly lower compared with the WT-CDAHFD group. Furthermore, the Gclc mRNA and phosphorylated protein kinase B (Akt) levels were significantly lower in the KO-ND group compared with the WT-ND group. The results of the current study indicated that as NASH progressed in the absence of renalase, oxidative stress, macrophage infiltration and TGF-β expression were enhanced, while α-SMA expression in NASH may be partly suppressed due to the decreased phosphorylation of Akt level.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Effects of renalase deficiency on liver fibrosis markers in a nonalcoholic steatohepatitis mouse model

et al. 2021

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“…ABCC4 participates in bile acid transport, which is related to oxidative stress, inflammation (Allen et al, 2011) and fibrosis (Suga et al, 2019). It was found that the expression of ABCC4 was increased significantly during the development of NASH (Suga et al, 2019). ITGB2 participates in cell adhesion, which plays an important role in the inflammatory response in NAFLD (Hou et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The above results showed that the hub miRNAs and their potential target genes are involved in immunity/inflammation or oxidative response. It is beyond doubt that inflammation and oxidative stress are vital mechanisms in the formation and progression of NASH (Li et al, 2016). Inflammation is one of the hallmarks of NASH and innate immune activation is a core FXR/RXR Activation Cellular functions and signal transduction mmu-let-7a-5p,mmu-let-7b-5p PD-1, PD-L1 cancer immunotherapy pathway Inflammation/immunity mmu-let-7a-5p,mmu-let-7b-5p PXR/RXR Activation Cellular functions and signal transduction mmu-let-7a-5p,mmu-let-7b-5p…”

Section: Discussionmentioning

confidence: 99%

The Target MicroRNAs and Potential Underlying Mechanisms of Yiqi-Bushen-Tiaozhi Recipe against‐Non-Alcoholic Steatohepatitis

Wang

Cai

et al. 2020

Front. Pharmacol.

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MicroRNAs (miRNAs) have emerged as potential therapeutic targets for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Traditional Chineses Medicine (TCM) plays an important role in the prevention or treatment of NAFLD/NASH. However, miRNA targets of TCM against NASH still remain largely unknown. Here, we showed that Yiqi-Bushen-Tiaozhi (YBT) recipe effectively attenuated diet-induced NASH in C57BL/6 mice. To identify the miRNA targets of YBT and understand the potential underlying mechanisms, we performed network pharmacology using miRNA and mRNA deep sequencing data combined with Ingenuity Pathway Analysis (IPA). Mmu-let-7a-5p, mmu-let-7b-5p, mmu-let-7g-3p and mmu-miR-106b-3p were screened as the main targets of YBT. Our results suggested that YBT might alleviate NASH by regulating the expression of these miRNAs that potentially modulate inflammation/immunity and oxidative stress. This study provides useful information for guiding future studies on the mechanism of YBT against NASH by regulating miRNAs.

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“…Therefore, Maekawa et al developed a novel method for searching conjugated cholesterol metabolites to identify more accurate diagnostic candidates. Conjugated cholesterol metabolites, including bile acid conjugates, can be analyzed with high sensitivity via LC/ESI-MS/MS [68][69][70][71][72]. In addition, it is well-known that abnormal conjugated cholesterol metabolites are found in many of cholesterol-related metabolic disorders and hepatobiliary diseases [73,74].…”

Section: Abnormal Cholenoic Acidsmentioning

confidence: 99%

Identification and Evaluation of Biomarkers for Niemann-Pick Disease Type C Based on Chemical Analysis Techniques

Maekawa

Mano

2020

Chromatography

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Niemann-Pick disease type C (NPC) is an autosomal recessive disorder that features progressive neurodegeneration. Because NPC patients have mutations in NPC1 or NPC2 cholesterol transporting proteins, failures in cholesterol and other lipid trafficking occur. NPC patients represent a wide clinical spectrum in terms of age of onset and type of symptoms. Because conventional diagnostic methods are time-consuming and complicated, biomarker tests have attracted increased attention. In this review, recently reported biomarkers for NPC are discussed in detail. For example, oxysterols and some cholenoic acid conjugates, metabolized from excess cholesterol in NPC cells, can be detected in urine or plasma. In addition, two types of lysosphingolipids, sphingosylphosphorylcholine and glycosylsphingosine, are present at increased concentrations in NPC patients.A more recently discovered biomarker is N-palmitoyl-O-phosphorylcholine, previously called "lysosphingomyelin-509." These biomarkers are helpful for the early diagnosis of NPC and may contribute to a good prognosis for NPC patients.

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Altered bile acid composition and disposition in a mouse model of non-alcoholic steatohepatitis

Cited by 54 publications

References 47 publications

Effects of renalase deficiency on liver fibrosis markers in a nonalcoholic steatohepatitis mouse model

Effects of renalase deficiency on liver fibrosis markers in a nonalcoholic steatohepatitis mouse model

The Target MicroRNAs and Potential Underlying Mechanisms of Yiqi-Bushen-Tiaozhi Recipe against‐Non-Alcoholic Steatohepatitis

Identification and Evaluation of Biomarkers for Niemann-Pick Disease Type C Based on Chemical Analysis Techniques

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