title: Supplementation of sodium butyrate protects mice from the development of non-alcoholic steatohepatitis (NASH).
abstract: Overnutrition, insulin resistance and an impaired intestinal barrier function are discussed as critical factors in the development of non-alcoholic fatty liver disease. Not only butyrate-producing probiotics as well as supplementation of sodium butyrate (SoB) have been suggested to bear protective effects on liver damage of various aetiologies. However, whether an oral consumption of SoB has a protective effect on Western-style diet (WSD)-induced non-alcoholic steatohepatitis (NASH) and if so molecular mechanism involved has not yet been determined. Eight-week-old C57BL/6J mice were pair-fed either a liquid control or WSD±0·6 g/kg body weight SoB. After 6 weeks, markers of liver damage, inflammation, toll-like receptor (TLR)-4 signalling, lipid peroxidation and glucose as well as lipid metabolism were determined in the liver tissue. Tight junction protein levels were determined in the duodenal tissue. SoB supplementation had no effects on the body weight gain or liver weight of WSD-fed mice, whereas liver steatosis and hepatic inflammation were significantly decreased (e.g. less inflammatory foci and neutrophils) when compared with mice fed only a WSD. Tight junction protein levels in duodenum, hepatic mRNA expression of TLR-4 and sterol regulatory element-binding protein 1c were altered similarly in both WSD groups when compared with controls, whereas protein levels of myeloid differentiation primary response gene 88, inducible nitric oxide synthase, 4-hydroxynonenal protein adducts and F4/80 macrophages were only significantly induced in livers of mice fed only the WSD. In summary, these data suggest that an oral supplementation of SoB protects mice from inflammation in the liver and thus from the development of WSD-induced NASH.
authors.affiliation: Institute of Nutritional Sciences,SD Model Systems of Molecular Nutrition,Friedrich-Schiller-University Jena,07743 Jena,Germany.
authors.forename: Cheng Jun
authors.initials: CJ
authors.lastname: Jin
authors.affiliation: Institute of Nutritional Sciences,SD Model Systems of Molecular Nutrition,Friedrich-Schiller-University Jena,07743 Jena,Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Sellmann
authors.affiliation: Institute of Nutritional Sciences,SD Model Systems of Molecular Nutrition,Friedrich-Schiller-University Jena,07743 Jena,Germany.
authors.forename: Anna Janina
authors.initials: AJ
authors.lastname: Engstler
authors.affiliation: Institute of Nutritional Sciences,SD Model Systems of Molecular Nutrition,Friedrich-Schiller-University Jena,07743 Jena,Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Ziegenhardt
authors.affiliation: Institute of Nutritional Sciences,SD Model Systems of Molecular Nutrition,Friedrich-Schiller-University Jena,07743 Jena,Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D020148:Butyric Acid / Q000627:therapeutic use*; D066273:Diet, Western / Q000009:adverse effects; D019587:Dietary Supplements; D004386:Duodenum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D065626:Non-alcoholic Fatty Liver Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D005765:Gastrointestinal Agents; D062725:Tight Junction Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D020148:Butyric Acid
keywords: Hepatic inflammation; Inducible nitric oxide synthase; Non-alcoholic fatty liver disease; Reactive oxygen species; Sodium butyrate