Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development

Journal of Hepatology, Journal Year: 2019, Volume and Issue: 71(6), P. 1216 - 1228

Published: Aug. 13, 2019

•During diet-induced dysbiosis the gut vascular barrier is disrupted.•Gut disruption responsible for translocation of bacteria or bacterial products systemically.•Inhibiting prevents development non-alcoholic steatohepatitis.•Obeticholic acid can control both in a preventive and therapeutic way. Background & AimsFatty liver disease, including fatty (NAFLD) steatohepatitis (NASH), has been associated with increased intestinal permeability into blood circulation. In this study, we aimed to unravel role integrity microbiota NAFLD/NASH development.MethodsC57BL/6J mice were fed high-fat diet (HFD) methionine-choline-deficient 1 week longer recapitulate aspects NASH (steatosis, inflammation, insulin resistance). Genetic pharmacological strategies then used modulate integrity.ResultsWe show that epithelial (GVB) are early events pathogenesis. Mice HFD only undergo drives GVB damage liver. Fecal transplantation from HFD-fed specific pathogen-free recipients induces epididymal adipose tissue enlargement. depends on interference WNT/β-catenin signaling pathway, as shown by genetic intervention driving β-catenin activation endothelial cells, preventing development. The bile analogue farnesoid X receptor agonist obeticholic (OCA) cells. Accordingly, pharmacologic OCA protects against disruption, agent. Importantly, found upregulation leakage marker colon patients NASH.ConclusionsWe have identified new player development, GVB, whose leads product Treatment at restoring such administration OCA, development.Lay summaryThe incidence disease reaching epidemic levels USA, more than 30% adults having NAFLD (non-alcoholic disease), which progress severe (NASH). Herein, NASH. We drug thereby NASH, providing further evidence its use prevention treatment Fatty C57BL/6J integrity.

Language: Английский

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Nonalcoholic Fatty Liver Disease in Lean Individuals in the United States

Medicine, Journal Year: 2012, Volume and Issue: 91(6), P. 319 - 327

Published: Nov. 1, 2012

The presence of hepatic steatosis in individuals without a known cause chronic liver disease, including excessive alcohol consumption, is the hallmark nonalcoholic fatty disease (NAFLD). Although NAFLD usually associated with obesity, nonobese patients can also present ("lean NAFLD"). Our objective was to determine factors independently lean United States population. For this purpose, we used data from National Health and Nutrition Examination Survey III (NHANES III) conducted between 1988 1994 available ultrasound, clinico-demographic, laboratory data. defined as moderate-severe (by ultrasound), absence use (>20 g/d men 10 women), hepatitis B surface antigen(−), C antibody(−). Nonalcoholic steatohepatitis (NASH) having elevated aminotransferases type 2 diabetes or insulin resistance (IR). Logistic regression identify independent predictors NAFLD. As result, 11,613 participants included study, 2185 (18.77% ± 0.76%) had NAFLD; these, 307 (11.78% 1.03%) NASH. Multivariate analysis showed that younger age, female sex, decreased likelihood IR hypercholesterolemia (p values < 0.05). Additionally, multivariate NASH being Hispanic, components metabolic syndrome such hypertension Therefore, conclude have different clinical profile than overweight-obese Furthermore, are commonly Hispanic syndrome.

Language: Английский

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Expanding Roles for Lipid Droplets

Current Biology, Journal Year: 2015, Volume and Issue: 25(11), P. R470 - R481

Published: June 1, 2015

Language: Английский

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ER Stress Cooperates with Hypernutrition to Trigger TNF-Dependent Spontaneous HCC Development

Cancer Cell, Journal Year: 2014, Volume and Issue: 26(3), P. 331 - 343

Published: Aug. 14, 2014

Language: Английский

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The role of hepatokines in metabolism

Nature Reviews Endocrinology, Journal Year: 2013, Volume and Issue: 9(3), P. 144 - 152

Published: Jan. 22, 2013

Language: Английский

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