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Oral arginine supplementation protects female mice from the onset of non-alcoholic steatohepatitis.

ABSTRACT: Dietary arginine (Arg) supplementation has been proposed to have positive effects on the development of liver diseases. In the present study, we investigate if an oral Arg supplementation in diet protects mice fed a fructose, fat and cholesterol enriched Western-style diet (WSD) from the development of non-alcoholic steatohepatitis (NASH). Female C57BL/6J mice were fed a liquid control diet or a liquid WSD ± Arg (2.49 g/kg body weight/day) for 6 weeks. Indices of liver injury, glucose metabolism and intestinal permeability were determined. While Arg supplementation had no effects on body weight gain, fasting blood glucose levels were significantly lower in WSD+Arg-fed mice than in C+Arg-fed animals. WSD-fed mice developed liver steatosis accompanied with inflammation, both being significantly attenuated in WSD+Arg-fed mice. These effects of Arg supplementation went along with a protection against WSD-induced decreased tight junction protein levels in the upper parts of the small intestine, increased levels of bacterial endotoxin in portal plasma as well as increased hepatic toll-like receptor-4 mRNA and 4-hydroxynonenal protein adduct levels. In conclusion, Arg supplementation may protect mice from the development of NASH.

SUBMITTER: Sellmann C

PROVIDER: S-EPMC5487836 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Oral arginine supplementation protects female mice from the onset of non-alcoholic steatohepatitis.

Sellmann Cathrin C Degen Christian C Jin Cheng Jun CJ Nier Anika A Engstler Anna Janina AJ Hasan Alkhatib Dana D De Bandt Jean-Pascal JP Bergheim Ina I

Amino acids 20170422 7

Dietary arginine (Arg) supplementation has been proposed to have positive effects on the development of liver diseases. In the present study, we investigate if an oral Arg supplementation in diet protects mice fed a fructose, fat and cholesterol enriched Western-style diet (WSD) from the development of non-alcoholic steatohepatitis (NASH). Female C57BL/6J mice were fed a liquid control diet or a liquid WSD ± Arg (2.49 g/kg body weight/day) for 6 weeks. Indices of liver injury, glucose metabolism ...[more]

PMID: 28434046

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Project description:BackgroundYinzhihuang (YZH) oral liquid is a traditional Chinese medicine compound that has emerged as a promising therapeutic agent for non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the therapeutic effects of YZH on non-alcoholic steatohepatitis (NASH) and elucidate its underlying molecular mechanisms.MethodsMice fed on a high-fat diet plus fructose/glucose drinking water (HFGD) were treated with YZH (30 mL/kg/d). The effects of YZH on mice with NASH were assessed through serological analysis and histological examination. Microbiota analysis based on 16S ribosomal ribonucleic acid (16S rRNA) and intestinal mucosal barrier function, serum inflammatory factors, hepatic macrophage infiltration, as well as hepatic toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NFκB) pathway were carried out to explore the mechanism of YZH for treatment of NASH.ResultsResults of the current study found that YZH effectively reduced body weight gain and adiposity and alleviated hepatocyte steatosis, hepatocyte ballooning, liver tissue lobular inflammation, as well as fibrosis. It also reduced the accumulation of triglycerides, cholesterol, and free fatty acids in the liver of the treated mice and normalized serum aspartate transaminase, alanine transaminase, and glucose levels as well as lipid metabolism. Meanwhile, YZH treatment significantly decreased the abundance of harmful bacteria, such as Mucispirillum, Helicobacter, and Desulfovibrionaceae. Mechanistically, the present study found that YZH upregulated the expression of tight junction proteins, decreased serum lipopolysaccharide, interleukin 6, and tumor necrosis factor α levels, and increased interleukin 10 levels in serum. In the liver, YZH alleviated macrophage infiltration, especially that of pro-inflammatory macrophages. Moreover, it was found that YZH inhibited the canonical TLR4, MyD88, NFκB signaling pathway.ConclusionsIn conclusion, YZH may be a new agent for the prevention of NASH. Further, YZH alleviates gut microbiota dysbiosis, restores the intestinal mucosal barrier, and inhibits the canonical TLR4, MyD88, NFκB signaling pathway.

Project description:This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.

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Oral arginine supplementation protects female mice from the onset of non-alcoholic steatohepatitis.

Publications

Oral arginine supplementation protects female mice from the onset of non-alcoholic steatohepatitis.

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