A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice

Wang, Xiaojing; Tanaka, Naoki; Hu, Xiao; Lu, Yu; Jia, Fangping; Sato, Yoshiko; Nakayama, Jun; Moriya, Kyoji; Koike, Kazuhiko; Aoyama, Toshifumi

doi:10.1007/s00204-019-02440-7

Cited by 22 publications

(34 citation statements)

References 38 publications

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“…[ 54 ] HFD can stimulate the nuclear translocation of NF‐κB p65, which promotes the occurrence of liver fibrosis and liver tumor. [ 55 ] In this study, the supplementation of LCP or Vc inhibited the nuclear translocation of NF‐κB p65 in the liver. p38 and JNK, which are involved in the MAPK signaling pathway, are important signal transmitters that transduce signals from the cell surface to the nucleus.…”

Section: Discussionmentioning

confidence: 72%

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress‐Induced Intestinal Environment Imbalance and Lipopolysaccharide‐Induced Liver Injury in HFD‐Fed Rats by Regulating the Nrf2/HO‐1/NQO1 and MAPK Pathways

Cheng

Sun

et al. 2020

Molecular Nutrition Food Res

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Scope: This study investigates the modulatory effects of Lonicera caerulea L. polyphenols (LCPs) on the intestinal environment and lipopolysaccharide (LPS)-induced liver injury via the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (HO-1)/NQO1 and mitogen-activated protein kinase (MAPK) pathways in a rat model of oxidative stress damage (OSD). Methods and results: To examine the prebiotic properties of LCP, a model of high-fat-diet-induced OSD is established using Sprague Dawley rats. In the colon, treatment with LCP for 8 weeks ameliorates enhanced intestinal permeability (glucagon-like peptide-2 content and occludin protein increase, whereas claudin-2 protein decreases), intestinal inflammation (levels of pro-inflammatory cytokines, such as tumor necrosis factor-, interleukin-6, cyclooxygenase-2, and nuclear factor kappa-B p65 (NF-B p65), decrease), and intestinal OSD (through regulation of the Nrf2/HO-1/NQO1 pathway). Moreover, LCP alleviates LPS-induced liver injury by suppressing the nuclear translocation of NF-B p65 and activation of the MAPK signaling pathway. Additionally, Bacilli, Lactobacillales, Lactobacillaceae, Lactobacillus, Akkermansia, Actinobacteria, Proteobacteria, Rothia, and Blautia are found to be the key intestinal microbial taxa related to intestinal OSD and LPS-induced liver injury in rats. Conclusion: LCP treatment potentially modulates the intestinal environment and alleviates liver injury by suppressing oxidative-stress-related pathways and altering the composition of the intestinal microbiota.

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Section: Discussionmentioning

confidence: 72%

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress‐Induced Intestinal Environment Imbalance and Lipopolysaccharide‐Induced Liver Injury in HFD‐Fed Rats by Regulating the Nrf2/HO‐1/NQO1 and MAPK Pathways

Cheng

Sun

et al. 2020

Molecular Nutrition Food Res

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“…The diet was purchased from Research Diets Inc. (New Brunswick, NJ, USA). Mice in the former group were also used as the controls in the other studies [16,17]. A 30% decrease in food was selected as the DR intervention for the following two reasons: (1) a 30% food reduction protocol was reported to attenuate obesity and improve metabolic profiles without malnutrition in previous studies [10,11]; (2) this DR dose maintained the mouse body weight constant for the long term, preventing age-dependent body weight gain as determined by preliminary studies.…”

Section: Mice and Treatmentmentioning

confidence: 99%

“…Total liver lipids were extracted according to the hexane:isopropanol method [18] and measured using the identical kits (Wako Pure Chemical Industries Ltd). Hepatic hydroxyproline concentrations were measured using the QuickZyme Hydroxyproline Assay kit (QuickZyme BioSciences, Leiden, The Netherlands) as described elsewhere [16,17].…”

Section: Biochemical Analysismentioning

confidence: 99%

“…Total liver RNA was extracted using NucleoSpin RNA Plus Kit (Macherey-Nagel GmbH & Co. KG, Düren, Germany) and cDNA was reverse-transcribed with ReverTra Ace ® quantitative polymerase chain reaction (qPCR) RT Master Mix (Toyobo, Osaka, Japan). The levels of mRNA were quantified using an SYBR qPCR kit (Toyobo) and Applied Biosystems StepOne Plus Real-time PCR system (Thermo Fisher Scientific Inc., Waltham, MA, USA) [16][17][18][19][20][21][22]. One microliter of cDNA aliquots was added to each well.…”

Section: Quantitative Polymerase Chain Reaction Analysismentioning

confidence: 99%

“…The protein concentration was measured using a BCA Protein Assay Kit (Pierce Biotechnology, Rockford, IL, USA). Whole liver homogenates (25-50 μg protein in each lane) were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at a polyacrylamide gel concentration of 7.5-15% [14][15][16][17][18][19][20][21][22][23][24]. Nuclear fractions (21 μg of protein in each lane) were separated using 10% SDS-PAGE for assessing nuclear factor-kappa B (NF-κB) p65 component and peroxisome proliferator-activated receptor-α (PPARα).…”

Section: Immunoblot Analysismentioning

confidence: 99%

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Dietary Restriction Suppresses Steatosis-Associated Hepatic Tumorigenesis in Hepatitis C Virus Core Gene Transgenic Mice

et al. 2020

Self Cite

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Background and Aims: Dietary restriction (DR) is a preventive strategy for obesity, metabolic syndrome, cardiovascular disease, and diabetes. Although an interconnection between obesity, metabolic syndrome, fatty liver, and hepatocellular carcinoma has been documented, the mechanism and impact of DR on steatosis-derived hepatocarcinogenesis are not fully understood. This study aimed to evaluate whether DR can prevent hepatic tumorigenesis. Methods: Male hepatitis C virus core gene transgenic (HCVcpTg) mice that develop spontaneous age-dependent insulin resistance, hepatic steatosis, and ensuing liver tumor development without apparent hepatic fibrosis, were fed with either a control diet ad libitum (control group) or 70% of the same control diet (DR group) for 15 months, and liver phenotypes were investigated. Results: DR significantly reduced the number and volume of liver tumors. DR attenu

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Bifidobacterium longumBL‐19 inhibits oxidative stress and inflammatory damage in the liver of mice with NAFLD by regulating the production of butyrate in the intestine

Zhang,

Xu,

Dong

et al. 2024

Food Science & Nutrition

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Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, but there is currently no effective treatment method. Probiotics have been used as an adjunct therapy for NAFLD, but the mechanism is not clear. This study used Bifidobacterium longum BL19 (BL‐19) to treat the NAFLD mice induced by a high‐fat diet, and explored the treatment mechanism through gut microbiota and serum metabolomics techniques. We found that BL‐19 effectively prevented rapid weight gain in NAFLD mice and reduced their overall food and energy intake, decreased liver inflammatory factors expressions, and increased the bile acid synthetase enzyme CYP7A1 and superoxide dismutase. After BL‐19 treatment, the abundances of butyric acid bacteria (Oscillospira and Coprococcus) in the feces of mice increased significantly, and the concentration of butyric acid also increased significantly. We believe that BL‐19 promotes the production of butyrate in the intestines, which in turn regulates the activity of CYP7A1 in the liver and bile acid synthesis, ultimately treating liver inflammation and lipid accumulation in NAFLD mice. Serum metabolomics results indicated that BL‐19 affected multiple pathways related to inflammation and lipid metabolism in NAFLD mice. These findings suggest that BL‐19 shows promise as an adjunct therapy for NAFLD, as it can significantly improve oxidative stress, reduce inflammation in the liver, and decrease lipid accumulation.

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A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice

Cited by 22 publications

References 38 publications

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress‐Induced Intestinal Environment Imbalance and Lipopolysaccharide‐Induced Liver Injury in HFD‐Fed Rats by Regulating the Nrf2/HO‐1/NQO1 and MAPK Pathways

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress‐Induced Intestinal Environment Imbalance and Lipopolysaccharide‐Induced Liver Injury in HFD‐Fed Rats by Regulating the Nrf2/HO‐1/NQO1 and MAPK Pathways

Dietary Restriction Suppresses Steatosis-Associated Hepatic Tumorigenesis in Hepatitis C Virus Core Gene Transgenic Mice

Bifidobacterium longumBL‐19 inhibits oxidative stress and inflammatory damage in the liver of mice with NAFLD by regulating the production of butyrate in the intestine

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