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Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice.

ABSTRACT: The fibroblast cell line of 3T3-L1 was used as a cell model for screening and evaluating the feasibility of probiotic components in improving animal lipid metabolisms. The extracts from 12 Lactobacillus strains caused significantly reduced triacylglycerol (TAG) accumulation but with severe inflammation induction in 3T3-L1 adipocytes. Interestingly, exopolysaccharides (EPS) from LGG (Lactobacillus rhamnosus GG) significantly decreased the TAG accumulation without any inflammation. The anti-obesity effect of EPS was confirmed in high-fat-diets feeding mice. Fat pads of mice injected with EPS (50?mg/kg) every two days for two weeks were significantly reduced with much smaller adipocytes, compared with the counterparts. The levels of TAG and cholesterol ester in liver, as well as serum TAG, were decreased in EPS injected mice. In addition, down-regulated inflammation was observed in adipose tissue and liver. Interestingly, the expression of TLR2 in adipose tissue and 3T3-L1 cells was significantly increased by EPS addition. Moreover, the reverse of TAG accumulation in TLR2 knockdown 3T3-L1 in the presence of EPS confirmed that the inhibition effect of EPS on adipogenesis was mediated by TLR2. EPS from LGG has the potential for therapeutic development to intervene lipid metabolic disorders in mammals.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC5081535 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice.

Zhang Zhen Z Zhou Zhigang Z Li Yu Y Zhou Linkang L Ding Qianwen Q Xu Li L

Scientific reports 20161027

The fibroblast cell line of 3T3-L1 was used as a cell model for screening and evaluating the feasibility of probiotic components in improving animal lipid metabolisms. The extracts from 12 Lactobacillus strains caused significantly reduced triacylglycerol (TAG) accumulation but with severe inflammation induction in 3T3-L1 adipocytes. Interestingly, exopolysaccharides (EPS) from LGG (Lactobacillus rhamnosus GG) significantly decreased the TAG accumulation without any inflammation. The anti-obesit ...[more]

PMID: 27786292

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Project description:BackgroundLactobacillus rhamnosus GG (LGG) is the most widely used probiotic, but the mechanisms underlying its beneficial effects remain unresolved. Previous studies typically inoculated LGG in hosts with established gut microbiota, limiting the understanding of specific impacts of LGG on host due to numerous interactions among LGG, commensal microbes, and the host. There has been a scarcity of studies that used gnotobiotic animals to elucidate LGG-host interaction, in particular for gaining specific insights about how it modifies the metabolome. To evaluate whether LGG affects the metabolite output of pathobionts, we inoculated with LGG gnotobiotic mice containing Propionibacterium acnes, Turicibacter sanguinis, and Staphylococcus aureus (PTS).Results16S rRNA sequencing of fecal samples by Ion Torrent and MinION platforms showed colonization of germ-free mice by PTS or by PTS plus LGG (LTS). Although the body weights and feeding rates of mice remained similar between PTS and LTS groups, co-associating LGG with PTS led to a pronounced reduction in abundance of P. acnes in the gut. Addition of LGG or its secretome inhibited P. acnes growth in culture. After optimizing procedures for fecal metabolite extraction and metabolomic liquid chromatography-mass spectrometry analysis, unsupervised and supervised multivariate analyses revealed a distinct separation among fecal metabolites of PTS, LTS, and germ-free groups. Variables-important-in-projection scores showed that LGG colonization robustly diminished guanine, ornitihine, and sorbitol while significantly elevating acetylated amino acids, ribitol, indolelactic acid, and histamine. In addition, carnitine, betaine, and glutamate increased while thymidine, quinic acid and biotin were reduced in both PTS and LTS groups. Furthermore, LGG association reduced intestinal mucosal expression levels of inflammatory cytokines, such as IL-1α, IL-1β and TNF-α.ConclusionsLGG co-association had a negative impact on colonization of P. acnes, and markedly altered the metabolic output and inflammatory response elicited by pathobionts.

Project description:BackgroundSalmonella typhimurium (S.T), as an important foodborne bacterial pathogen, can cause diarrhea and gastroenteritis in humans and animals. Numerous studies have confirmed that exopolysaccharides (EPSs) have various biological functions, but the mechanism through which EPSs improve the immunity of animals against the invasion of pathogenic bacteria is unclear. Here, we explored the protective effect of EPSs of Lactobacillus rhamnosus GG (LGG) on the S.T-infected intestine.MethodsMice received adequate food and drinking water for one week before the start of the experiment. After 7 d of prefeeding, 2×108 CFU/mL S.T solution and an equivalent volume of saline (control group) were given orally for 1 d. On the fourth day, the mice were treated with 0.5 mg/mL EPSs, 1.0 mg/mL EPSs, 2.0 mg/mL EPSs, or 2.0 mg/mL penicillin for 7 d. Finally, the body and relative organ weight, histological staining, and the levels of antioxidant enzyme activity and inflammatory cytokines were determined.ResultsThe S.T-infected mice exhibited symptoms of decreased appetite, somnolence, diarrhea and flagging spirit. Treatment with EPSs and penicillin improved the weight loss of the mice, and the high dose of EPSs showed the best therapeutic effect. EPSs significantly ameliorated S.T-induced ileal injury in mice. High-dose EPSs were more effective than penicillin for alleviating ileal oxidative damage induced by S.T. The mRNA levels of inflammatory cytokines in the ileum of mice showed that the regulatory effects of EPSs on inflammatory cytokines were better than those of penicillin. EPSs could inhibit the expression and activation of key proteins of the TLR4/NF-κB/MAPK pathway and thereby suppress the level of S.T-induced ileal inflammation.ConclusionsEPSs attenuate S.T-induced immune responses by inhibiting the expression of key proteins in the TLR4/NF-κB/MAPK signaling pathway. Moreover, EPSs could promote bacterial aggregation into clusters, which may be a potential strategy for reducing the bacterial invasion of intestinal epithelial cells.

Dataset Information

Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice.

Publications

Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice.

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