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Lactobacillus paracasei Induces M2-Dominant Kupffer Cell Polarization in a Mouse Model of Nonalcoholic Steatohepatitis

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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).

Conflict of interest

The author(s) declare that they have no competing interests.

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Correspondence to Dae Won Jun.

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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

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