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Lipopolysaccharide induces adipose differentiation-related protein expression and lipid accumulation in the liver through inhibition of fatty acid oxidation in mice

  • Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

In the present study, we examined the effect of lipopolysaccharide (LPS) on liver histopathology with special reference to lipid metabolism in mice.

Methods

Mice were injected with LPS intraperitoneally, and its effect on the liver was investigated pathologically and biochemically.

Results

Oil-red O staining and adipose differentiation-related protein (ADRP) immunohistochemistry demonstrated that injection of LPS transiently induced lipid accumulation and ADRP expression in hepatocytes, especially around the portal vein. Microscopic observation revealed that lipid accumulation started 12 h after LPS injection. Time-course studies showed that LPS rapidly, within 2 h, decreased hepatic expression of nuclear hormone receptors, including peroxisome proliferator-activated receptor (PPAR) α. LPS inhibited the expression of PPARα-target genes involved in fatty acid oxidation in the liver such as those coding for enoyl-CoA hydratase, acyl-CoA dehydrogenase, and carnitine palmitoyl transferase-1, whereas LPS also suppressed the expression of genes related to fatty acid synthesis such as those for fatty acid synthase, stearoyl-CoA desaturase, and acetyl-CoA carboxylase α.

Conclusions

LPS induces transient lipid accumulation and expression of ADRP in the liver through inhibition of fatty acid oxidation by downregulation of the PPARα-related transcriptional mechanism.

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Authors and Affiliations

  1. Department of General Medicine, Asahikawa Medical College, 2-1 Midorigaoka-higashi, Asahikawa, 078-8510, Japan

    Masumi Ohhira, Mitsuko Fukuda, Nobuhiko Takahashi, Satoshi Tanno, Shima Kumei & Toshikatsu Okumura

  2. Department of Microbiology, Asahikawa Medical College, Asahikawa, Japan

    Wataru Motomura, Takayuki Yoshizaki & Nobutaka Wakamiya

  3. Department of Medicine, Asahikawa Medical College, Asahikawa, Japan

    Yutaka Kohgo

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  1. Masumi Ohhira
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  2. Wataru Motomura
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  3. Mitsuko Fukuda
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  10. Toshikatsu Okumura
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Ohhira, M., Motomura, W., Fukuda, M. et al. Lipopolysaccharide induces adipose differentiation-related protein expression and lipid accumulation in the liver through inhibition of fatty acid oxidation in mice. J Gastroenterol 42, 969–978 (2007). https://doi.org/10.1007/s00535-007-2119-8

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  • DOI: https://doi.org/10.1007/s00535-007-2119-8

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