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Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.

Publication ,  Journal Article
Li, Z; Yang, S; Lin, H; Huang, J; Watkins, PA; Moser, AB; Desimone, C; Song, X-Y; Diehl, AM
Published in: Hepatology
February 2003

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.

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Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

February 2003

Volume

37

Issue

2

Start / End Page

343 / 350

Location

United States

Related Subject Headings

  • Uncoupling Protein 2
  • Tumor Necrosis Factor-alpha
  • RNA, Messenger
  • Proteins
  • Probiotics
  • Oxidation-Reduction
  • Obesity
  • NF-kappa B
  • Mitogen-Activated Protein Kinases
  • Mitochondrial Proteins
 

Citation

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Chicago
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MLA
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Li, Z., Yang, S., Lin, H., Huang, J., Watkins, P. A., Moser, A. B., … Diehl, A. M. (2003). Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology, 37(2), 343–350. https://doi.org/10.1053/jhep.2003.50048
Li, Zhiping, Shiqi Yang, Huizhi Lin, Jiawen Huang, Paul A. Watkins, Ann B. Moser, Claudio Desimone, Xiao-yu Song, and Anna Mae Diehl. “Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.Hepatology 37, no. 2 (February 2003): 343–50. https://doi.org/10.1053/jhep.2003.50048.
Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003 Feb;37(2):343–50.
Li, Zhiping, et al. “Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.Hepatology, vol. 37, no. 2, Feb. 2003, pp. 343–50. Pubmed, doi:10.1053/jhep.2003.50048.
Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, Desimone C, Song X-Y, Diehl AM. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003 Feb;37(2):343–350.
Journal cover image

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

February 2003

Volume

37

Issue

2

Start / End Page

343 / 350

Location

United States

Related Subject Headings

  • Uncoupling Protein 2
  • Tumor Necrosis Factor-alpha
  • RNA, Messenger
  • Proteins
  • Probiotics
  • Oxidation-Reduction
  • Obesity
  • NF-kappa B
  • Mitogen-Activated Protein Kinases
  • Mitochondrial Proteins