Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease
| Autor: | Ann B. Moser, Xiao Yu Song, Huizhi Lin, Jiawen Huang, Shiqi Yang, Paul A. Watkins, Anna Mae Diehl, Zhiping Li, Claudio DeSimone |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Antibodies Ion Channels Hepatitis Mitochondrial Proteins Mice Insulin resistance Internal medicine Nonalcoholic fatty liver disease medicine Animals Uncoupling Protein 2 Obesity RNA Messenger chemistry.chemical_classification Hepatology biology Tumor Necrosis Factor-alpha Probiotics Insulin Fatty Acids Fatty liver JNK Mitogen-Activated Protein Kinases NF-kappa B Membrane Transport Proteins Proteins Fatty acid Alanine Transaminase DNA medicine.disease Dietary Fats Fatty Liver Mice Inbred C57BL Endocrinology Liver chemistry Alanine transaminase biology.protein Alcoholic fatty liver Insulin Resistance Mitogen-Activated Protein Kinases Steatosis Oxidation-Reduction |
| Zdroj: | Hepatology. 37:343-350 |
| ISSN: | 0270-9139 |
| DOI: | 10.1053/jhep.2003.50048 |
| Popis: | Ob/ob mice, a model for nonalcoholic fatty liver disease (NAFLD), develop intestinal bacterial overgrowth and overexpress tumor necrosis factor alpha (TNF-alpha). In animal models for alcoholic fatty liver disease (AFLD), decontaminating the intestine or inhibiting TNF-alpha improves AFLD. Because AFLD and NAFLD may have a similar pathogenesis, treatment with a probiotic (to modify the intestinal flora) or anti-TNF antibodies (to inhibit TNF-alpha activity) may improve NAFLD in ob/ob mice. To evaluate this hypothesis, 48 ob/ob mice were given either a high-fat diet alone (ob/ob controls) or the same diet + VSL#3 probiotic or anti-TNF antibodies for 4 weeks. Twelve lean littermates fed a high-fat diet served as controls. Treatment with VSL#3 or anti-TNF antibodies improved liver histology, reduced hepatic total fatty acid content, and decreased serum alanine aminotransferase (ALT) levels. These benefits were associated with decreased hepatic expression of TNF-alpha messenger RNA (mRNA) in mice treated with anti-TNF antibodies but not in mice treated with VSL#3. Nevertheless, both treatments reduced activity of Jun N-terminal kinase (JNK), a TNF-regulated kinase that promotes insulin resistance, and decreased the DNA binding activity of nuclear factor kappaB (NF-kappaB), the target of IKKbeta, another TNF-regulated enzyme that causes insulin resistance. Consistent with treatment-related improvements in hepatic insulin resistance, fatty acid beta-oxidation and uncoupling protein (UCP)-2 expression decreased after treatment with VSL#3 or anti-TNF antibodies. In conclusion, these results support the concept that intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and NAFLD and suggest novel therapies for these common conditions. |
| Databáze: | OpenAIRE |
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