Nonalcoholic Fatty Liver Disease and the Gut-Liver Axis: Exploring an Undernutrition Perspective

Bauer, Kylynda C.; Littlejohn, Paula; Ayala, Victòria; Creus-Cuadros, Anna; Finlay, B. Brett

doi:10.1053/j.gastro.2022.01.058

Cited by 63 publications

(49 citation statements)

References 185 publications

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“…In addition, prenatal fatty liver must provoke severe insulin resistance in the offspring of HFD-fed dams beginning early in life, accompanying the inhibition of insulin-stimulated glucose uptake. CD-feeding with insulin resistance after birth might lead to malnutrition, such as kwashiorkor and marasmus 51 , and exacerbate steatohepatitis.…”

Section: Discussionmentioning

confidence: 99%

A maternal high-fat diet induces fetal origins of NASH-HCC in mice

Takiyama

Sera

Nakamura

et al. 2022

Sci Rep

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Maternal overnutrition affects offspring susceptibility to nonalcoholic steatohepatitis (NASH). Male offspring from high-fat diet (HFD)-fed dams developed a severe form of NASH, leading to highly vascular tumor formation. The cancer/testis antigen HORMA domain containing protein 1 (HORMAD1), one of 146 upregulated differentially expressed genes in fetal livers from HFD-fed dams, was overexpressed with hypoxia-inducible factor 1 alpha (HIF-1alpha) in hepatoblasts and in NASH-based hepatocellular carcinoma (HCC) in offspring from HFD-fed dams at 15 weeks old. Hypoxia substantially increased Hormad1 expression in primary mouse hepatocytes. Despite the presence of three putative hypoxia response elements within the mouse Hormad1 gene, the Hif-1alpha siRNA only slightly decreased hypoxia-induced Hormad1 mRNA expression. In contrast, N-acetylcysteine, but not rotenone, inhibited hypoxia-induced Hormad1 expression, indicating its dependency on nonmitochondrial reactive oxygen species production. Synchrotron-based phase-contrast micro-CT of the fetuses from HFD-fed dams showed significant enlargement of the liver accompanied by a consistent size of the umbilical vein, which may cause hypoxia in the fetal liver. Based on these findings, a maternal HFD induces fetal origins of NASH/HCC via hypoxia, and HORMAD1 is a potential therapeutic target for NASH/HCC.

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Section: Discussionmentioning

confidence: 99%

A maternal high-fat diet induces fetal origins of NASH-HCC in mice

Takiyama

Sera

Nakamura

et al. 2022

Sci Rep

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“…NAFLD is closely raleted to metabolic syndrome and the pathogenesis of which is studied mainly based on metabonomics ( 11 , 12 ). In recent years, there is increasing evidence showing that the NAFLD related to the imbalance in intestinal flora ( 13 ). The latest study, recently published in science translational medicine, provides predictions of long-term NAFLD development based on clinical indicators of NAFLD patients, intestinal flora macrogenomics and metabonomics data ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

The contribution of the gut-liver axis to the immune signaling pathway of NAFLD

Liu

Cai

et al. 2022

Front. Immunol.

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Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of metabolic syndrome and is the most common chronic liver disease in the world. The pathogenesis of NAFLD has not been fully clarified; it involves metabolic disturbances, inflammation, oxidative stress, and various forms of cell death. The “intestinal-liver axis” theory, developed in recent years, holds that there is a certain relationship between liver disease and the intestinal tract, and changes in intestinal flora are closely involved in the development of NAFLD. Many studies have found that the intestinal flora regulates the pathogenesis of NAFLD by affecting energy metabolism, inducing endotoxemia, producing endogenous ethanol, and regulating bile acid and choline metabolism. In this review, we highlighted the updated discoveries in intestinal flora dysregulation and their link to the pathogenesis mechanism of NAFLD and summarized potential treatments of NAFLD related to the gut microbiome.

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“…It has been shown that NAFLD is strictly associated with alterations in gut microbiota and intestinal permeability [ 9 ]. This can, in turn, affect liver inflammation via the translocation of damage- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively) and, particularly of bacterial compounds (i.e., endotoxins), to the liver through portal circulation [ 10 ]. In this light, Escherichia Coli -derived lipopolysaccharide (LPS) has been identified as a driver of liver inflammation both in experimental models and in human NAFLD [ 11 ]; its deleterious effects are largely mediated by the activation of toll-like receptor 4 (TLR4) pathways within the liver [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…This can, in turn, affect liver inflammation via the translocation of damage- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively) and, particularly of bacterial compounds (i.e., endotoxins), to the liver through portal circulation [ 10 ]. In this light, Escherichia Coli -derived lipopolysaccharide (LPS) has been identified as a driver of liver inflammation both in experimental models and in human NAFLD [ 11 ]; its deleterious effects are largely mediated by the activation of toll-like receptor 4 (TLR4) pathways within the liver [ 10 ]. Therefore, the modulation of gut physiology and microbiota composition in NAFLD patients might represent a therapeutic approach to attenuate liver inflammation and, eventually, slow disease progression towards NASH.…”

Section: Introductionmentioning

confidence: 99%

Effect of Calcium-Sulphate-Bicarbonate Water in a Murine Model of Non-Alcoholic Fatty Liver Disease: A Histopathology Study

Carpino

Overi

Onori

et al. 2022

IJMS

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The progression of nonalcoholic fatty liver disease (NAFLD) is associated with alterations of the gut–liver axis. The activation of toll-like receptor 4 (TLR4) pathways by endotoxins, such as lipopolysaccharide (LPS), contributes to liver injury. The aim of the present study was to evaluate the possible beneficial effects of a calcium-sulphate-bicarbonate natural mineral water on the gut–liver axis by evaluating liver and terminal ileum histopathology in a murine model of NAFLD. NAFLD was induced in mice by administrating a methionine-choline-deficient (MCD) diet. The following experimental groups were evaluated: controls (N = 10); MCD+Tap water (MCD; N = 10); MCD+Calcium-sulphate-bicarbonate water (MCD/Wcsb; N = 10). Mice were euthanised after 4 and 8 weeks. Liver and terminal ileum samples were collected. Samples were studied by histomorphology, immunohistochemistry, and immunofluorescence. In mice subjected to the MCD diet, treatment with mineral water improved inflammation and fibrosis, and was associated with a reduced number of activated hepatic stellate cells when compared to MCD mice not treated with mineral water. Moreover, MCD/Wcsb mice showed lower liver LPS localization and less activation of TLR4 pathways compared to the MCD. Finally, Wcsb treatment was associated with improved histopathology and higher occludin positivity in intestinal mucosa. In conclusion, calcium-sulphate-bicarbonate water may exert modulatory activity on the gut–liver axis in MCD mice, suggesting potential beneficial effects on NAFLD.

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Nonalcoholic Fatty Liver Disease and the Gut-Liver Axis: Exploring an Undernutrition Perspective

Cited by 63 publications

References 185 publications

A maternal high-fat diet induces fetal origins of NASH-HCC in mice

A maternal high-fat diet induces fetal origins of NASH-HCC in mice

The contribution of the gut-liver axis to the immune signaling pathway of NAFLD

Effect of Calcium-Sulphate-Bicarbonate Water in a Murine Model of Non-Alcoholic Fatty Liver Disease: A Histopathology Study

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