Effect Of Lactobacillus Johnsonii BS15 On Fat Accumulation And NAFLD In High-fat Diet Induced Obesity Mice

To investigate the effect of Lactobacillus johnsonii BS15 on obesity and nonalcoholic fatty liver disease (NAFLD),120 male ICR mice were divided into two groups and administered with either PBS (PH 7.0) (ND group) or BS15 (daily amounts of either 2×107cfu, L-BS15 group; or 2×108cfu, H-BS15 group) by gavage throughout a 17-week experimental period. The mice were fed with normal chow diet (NCD) five weeks before the experimental period. After 35 days, The PBS group was also divided into ND and HFD groups. The diet of the HFD and BS15 groups was changed into high fat for the rest of the weeks. The sampling time points was 35,63,91,119 days of the experiment. Results were as follows:1. The body weight of the mice in HFD group was significant higher than ND group at the end of the experiment. Both doses of BS15 supplementation suppressedthe increase of body weight due to the high-fat diet consumption.2. Liver section from mice of HFD group exhibited visible intracellular vacuolization which marked lipid accumulation, but the degree of hepatic steatosis was appreciably attenuated by the treatment of BS15.3. The detection of liver apoptosis by flow cytometry (FCM) showed that the percentage of apoptotic cells in liver of HFD group was significantly increased compared with ND group, and the growth trend was inhibited by the supplementation of BS15.4. The results of RT-PCR quantification of microbial cecal content showed that the supplementation of BS15 significantly increased the abundance of Lactobacillus spp., L. johnsonii, and Bacteroidetes, and lowered the abundance of Enterobacteriaceae family and the ratio of Firmicutes/Bacteroidetes. The gut flora disturbance induced by high-fat diet was attenuated by the treatment of BS155. Lipid metabolism gene expression was detected though RT-PCR. Compared with ND group, the mRNA levels of ACC1, FAS and PPARγ were significantly increased in HFD group, the gene level of FIAF was markedly reduced. After the treatment of BS15, the mRNA levels of ACC1, FAS and PPARγ in BS15-group were apparently lowered in comparison with HFD group, and the level of FIAF was significantly increased.6. The gut permeability of mice in HFD group was significantly increased in comparison with ND group. After the treatment of BS15, the gut permeability of mice in BS15 group was reduced compared with HFD group.7. Compared with ND group, high-fat diet significantly induced a high serum level of LPS and a high expression of TNF-α in liver of HFD group at the end of the experiment. After the treatment of BS15, the serum level of LPS and the expression of TNF-α in liver of BS-15 group were markly lowered. From 63 days to 119 days, the serum level of CRP of HFD group was significantly higher than ND group, but the treatment of BS15 significantly inhibited the trend.8. High-fat diet apparently induced a IR in HFD group compared with ND group from 63 days to 119 days, and IR in BS15-group was significantly inhibited. The serum level of TG, TC, LDL-C, ALT and FFA in HFD-fed groups was significantly higher than those in ND-fed group at 119 days, but the supplementation of BS15 markedly reduced TG, LDL-C, ALT and FFA levels induced by high-fat diet. In addition, the HFD group exhibited a significant decrease in serum HDL-C levels in comparison with ND and BS15 groups.9. In comparison with ND group, the levels of H2O2, GSH, MDA in liver cytosolic and mitochondria were significantly increased in HFD group. However, administration of BS15 apparently lowered those indexes in liver cytosolic and mitochondria. Mice fed with HFD had lower CAT, GSH-PX and T-SOD activity in liver cytosolic and mitochondria in comparison with ND group. Compared with HFD group, both doses of BS15 supplementation raised CAT and GSH-PX activity in mitochondria, but the T-SOD activity was no changed. But the increase of T-SOD activity in liver cytosolic was found in both doses of BS15 supplementation compared with HFD group, while the significant increase of CAT and GSH-PX activity in liver cytosolic was only revealed in H-BS15 group.In conclusion, the treatment of L. johnsonii BS15 may have the ability of preventing the diet-induced obesity and NAFLD through adjusting gut flora and reducing the gut permeability, inflammation, IR and oxidative stress.