Abstract
Background and Aims
Gut microbiota may be associated with the pathogenesis of nonalcoholic steatohepatitis (NASH). This study aimed to investigate the protective effects and possible mechanisms of Lactobacillus paracasei on NASH.
Methods
Thirty male C57BL/6 mice were randomized into three groups and maintained for 10 weeks: control group (standard chow), NASH model group (high fat + 10 % fructose diet), and the L. paracasei group (NASH model with L. paracasei). Liver histology, serum aminotransferase levels, and hepatic gene expression levels were measured. Intestinal permeability was investigated using urinary 51Creatinine Ethylenediaminetetraacetic acid (51Cr-EDTA) clearance. Total Kupffer cell counts and their composition (M1 vs. M2 Kupffer cells) were measured using flow cytometry with F4/80 and CD206 antibodies.
Results
Hepatic fat deposition, serum ALT level, and 51Cr-EDTA clearance were significantly lower in the L. paracasei group than the NASH group (p < 0.05). The L. paracasei group had lower expression in Toll-like receptor-4 (TLR-4), NADPH oxidase-4 (NOX-4), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin 4 (IL-4), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-δ compared with the NASH group (p < 0.05). The total number of F4/80+ Kupffer cells was lower in the L. paracasei group than the NASH group. L. paracasei induced the fraction of F4/80+CD206+ cells (M2 Kupffer cells) while F4/80+CD206− cells (M1 Kupffer cells) were higher in the NASH group (F4/80+CD206+ cell: 44 % in NASH model group vs. 62 % in L. paracasei group, p < 0.05).
Conclusions
Lactobacillus paracasei attenuates hepatic steatosis with M2-dominant Kupffer cell polarization in a NASH model.
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Abbreviations
- NAFLD:
-
Nonalcoholic fatty liver disease
- TLR:
-
Toll-like receptors
- NASH:
-
Nonalcoholic steatohepatitis
- L. paracasei :
-
Lactobacillus paracasei
- AST:
-
Aspartate aminotransferase
- ALT:
-
Alanine aminotransferase
- H & E:
-
Hematoxylin and eosin stain
- NOX:
-
NADPH oxidase
- Cr:
-
Creatinine
- EDTA:
-
Ethylenediaminetetraacetic acid
- CD:
-
Cluster of differentiation
- TNF-α:
-
Tumor necrosis factor alpha
- MCP-1:
-
Monocyte chemotactic protein-1
- IL:
-
Interleukin
- PPAR-γ:
-
Peroxisome proliferator activated receptor gamma
- PPAR-δ:
-
Peroxisome proliferator activated receptor delta
- RT-PCR:
-
Reverse transcription polymerase chain reaction
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- SEM:
-
Standard error of the mean
- COX:
-
Cyclooxygenase
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Acknowledgments
This study was supported by a Grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A121185).
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The author(s) declare that they have no competing interests.
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Sohn, W., Jun, D.W., Lee, K.N. et al. Lactobacillus paracasei Induces M2-Dominant Kupffer Cell Polarization in a Mouse Model of Nonalcoholic Steatohepatitis. Dig Dis Sci 60, 3340–3350 (2015). https://doi.org/10.1007/s10620-015-3770-1
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DOI: https://doi.org/10.1007/s10620-015-3770-1