ABSTRACT
Objective To investigate the effectiveness of Lactobacillus paracasei N1115 combined with fructooligosaccharides (FOS) in the treatment of nonalcoholic fatty liver disease(NAFLD) in a mouse model and to analyze the possible mechanism.Methods Fifty male C57BL/6 mice were randomly divided into five groups and respectively given normal diet (ND group), high-fat diet (HFD group), HFD containing Lactobacillus paracasei N1115 (HFD+L) (2.2×109 CFU/ml), HFD containing FOS (HFD+FOS) (4 g/kg per day) and HFD containing Lactobacillus paracasei N1115 and FOS for 16 consecutive weeks.Levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lipopolysaccharide (LPS) and diamine oxidase (DAO) in serum samples from each group were measured.Expression of tight-junction proteins (Claudin-1 and Occludin), p38 and phosphorylated p38 (p-p38) in intestinal tissues were analyzed.Results Compared with the HFD group, the HFD+FOS+L group showed decreased levels of TC, TG, LDL, LPS and DAO in serum samples, but increased serum HDL level (P<0.05).Moreover, combined treatment with Lactobacillus paracasei N1115 and FOS alleviated liver lipid deposition, significantly increased the expression of Claudin-1 and Occludin in intestine and inhibited the phosphorylation of p38 (P<0.05).Conclusion Lactobacillus paracasei N1115 combined with FOS may increase the expression of Claudin-1 and Occludin through inhibiting the phosphorylation of intestinal p38, which is conducive to maintaining the intestinal mucosal barrier integrity and alleviating NAFLD.
ABSTRACT
Objective@#To investigate the effects of Lactobacillus paracasei N1115 combined with fructooligosaccharides (FOS) on non-alcoholic fatty liver disease (NAFLD) in mice and its possible mechanism.@*Methods@#A total of 50 male C57 mice were randomly and equally divided into five experimental groups. Group 1 received a normal diet (ND). Other four groups received a high-fat diet (HFD) to establish NAFLD models. In addition to HFD, group 3 received Lactobacillus paracasei N1115 (2.2×109 CFU/mL), group 4 received FOS (4 g/kg per day), and group 5 received Lactobacillus paracasei N1115 (2.2×109 CFU/mL) and FOS (4 g/kg per day). All groups received continuous intervention for 16 weeks. The following indices were measured for all groups after intervention: general condition, the levels of fasting blood glucose, insulin, and lipopolysaccharide (LPS), and the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ in the serum and liver. The mRNA levels of Toll-like receptor (TLR)4, nuclear factor (NF)-κb, insulin receptor (InsR), and insulin receptor substrate (IRS)-1 were measured by real-time RT-PCR. The data were subjected to one-way analysis of variance and comparison between groups was made by Bonferroni method.@*Results@#Compared with group 2, groups 3, 4, and 5 had significantly lower body weight, Lee's index, liver index, and the levels of blood glucose and insulin resistance (P < 0.05). The serum level of LPS in group 2 was significantly higher than that in the other experimental groups (group 1: 8.80 ± 0.85 U/L, group 3: 12.31 ± 1.01 U/L, group 4: 12.27 ± 0.98 U/L, and group 5: 10.17 ± 0.79 U/L vs group 2: 15.45 ± 1.14 U/L, F = 55.117, P < 0.001). The levels of TNF-α, IL-1β, IL-6, and IFN-γ in the serum and liver in group 2 were also significantly higher than those in the other groups (P < 0.05). Group 2 had significantly higher mRNA levels of TLR4 and NF-κb in the liver than the other groups (F = 82.933, P < 0.001; F = 149.033, P < 0.001); however, it had significantly lower mRNA levels of InsR and IRS-1 in the liver than the other groups (F = 33.347, P < 0.001; F = 70.225, P < 0.001).@*Conclusion@#Lactobacillus paracasei N1115 combined with FOS can reduce the level of LPS in the blood circulation, inhibit activation of the LPS/TLR4 signaling pathway, and reduce the release of inflammatory factor and the body's insulin resistance, so it can relieve NAFLD.