Regulation Of Lipid Metabolism By Cholesterol-lowerinng Lactic Acid Bacteria In Obese Mice

As a typical metabolic syndrome,obesity is closely related to disruption of lipid metabolism and energy metabolism.Obesity will also contribute to the pathogenesis of other chronic diseases.A large number of studies have shown that cholesterol metabolism is closely related to lipid metabolism,and the imbalance of the regulatory mechanism of lipid metabolism will affect cholesterol metabolism.In modern life,People’s unhealthy diet,especially long-term diet rich in sugar and fat is the main reasons for obesity.At present,drug therapy is the mainstream way to lose weight,but such drugs are expensive and may cause muscle damage,skin allergy,hyperuricemia and other adverse reactions.It is important and necessary to look for safe and effective non-drug therapy.Relevant reports have pointed out that lactic acid bacteria can help to improve hepatic lipid metabolism,and an appropriate amount of lactic acid bacteria supplement can effectively remove serum cholesterol and maintain the balance of lipid metabolism in the body.In this study,lactic acid bacteria with high cholesterol degradation rate were selected from fermented dairy products.A total of 7 strains were tested,including bile salt hydrolase(BSH)activity,gastrointestinal tolerance,surface hydrophobicity,self-aggregation ability,antioxidant activity,antibacterial activity and antibiotic sensitivity.Finally,high-fat dietinduced obesity mice were used to explore the in vivo cholesterol-reducing and lipidregulating mechanism.Here are the main findings and results:1、A total of 56 strains were screened from fermented dairy products and they were preliminarily identified as lactic acid bacteria by Gram staining and catalase experiments.The phthalaldehyde coloration method was used to evaluate the in vitro cholesterol-lowering ability of the above-mentioned tested strains,and the 8 strains numbered 111,352,482,4-11,55,66,N7 and Q16 were screened and their cholesterol degradation rate exceeded 20%.The 8 strains were identified by 16 S r DNA molecular biology method,and 111,352,482,4-11,55,and 66 were identified as Pediococcus lactis,and N7 and Q16 were Lactobacillus plantarum.2 、 Pediococcus lactis 352 had the highest cholesterol degradation rate,and Lactobacillus plantarum N7 and Lactobacillus plantarum Q16 were selected as experimental strains.Meanwhile,Lactobacillus reuteri A2,Lactobacillus casei A3 and Lactobacillus yoselii F3 were isolated as controls.The BSH activity,gastrointestinal tolerance,surface hydrophobicity,self-aggregation ability,antioxidant activity and antibacterial activity of 6strains were evaluated,5 strains including Lactobacillus casei A3,Lactobacillus johnsonii F3,Pediococcus lactis 352,Lactobacillus plantarum N7 and Lactobacillus plantarum Q16 with excellent comprehensive performance were screened out.They were used to the following animal experiment.3、The in vivo study adopts preventive therapy.The results show that the intervention of Lactobacillus plantarum Q16 is effective in alleviating obesity.Lactobacillus plantarum Q16 exhibited no toxic effect on mice and also had abilities to reduce body weight,the content of total cholesterol(TC),total triglyceride(TG)and low-density lipoprotein(LDLC)in serum and liver.However,the content of high-density lipoprotein(HDL-C)in serum and liver did not have significant difference.At the same time,Lactobacillus plantarum Q16 significantly reduced the activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)in the serum,further alleviating liver damage in obese mice.In addition,Lactobacillus plantarum Q16 can inhibit oxidative stress in obese mice by reducing the activity of catalase(CAT)and the content of propylene glycol(MDA)in the liver,and significantly increasing the activity of superoxide dismutase(SOD)in the serum.Finally,Lactobacillus plantarum Q16 can also significantly increase the content of bile acids in feces and promote the excretion of cholesterol in the form of bile acids.4 、 The fluorescence quantitative PCR method was used to evaluate the effect of Lactobacillus plantarum Q16 on the expression levels of AMPK,CPT-1,PPAR-γ,FIAF,LDL-R,ACC,and IL-1β in the liver of obese mice.Lactobacillus plantarum Q16 can significantly increase the expression levels of AMPK,CPT-1,PPAR-γ,FIAF,LDL-R,and reduce the expression levels of AMPK downstream targets ACC and inflammatory factor IL-1β.This strain also regulated hepatic lipid metabolism by reducing lipid accumulation in the liver.5、HE staining of intestinal tissue showed that Lactobacillus plantarum Q16 helped to maintain the integrity of intestinal tissue structure.High-throughput sequencing results showed that Lactobacillus plantarium Q16 could increase the abundance and diversity richness of intestinal microorganisms in mice.At the phylum level,the ratio of Bacteroidetes and Firmicutes(B/F)is significantly increased after treatment with Lactobacillus plantarium Q16.At the genus level,Lactobacillus plantarum Q16 increased the abundance of Akkermansia,Ruminococcus,Anaerostipes,Parabacteroides,and S24-7,but decreased the abundance of Alistipes,Oscillospira,Clostridiaceae,Odoribacteraceae,and Streptococcaceae.Taken together,it is obvious that Lactobacillus plantarum Q16 can regulate the intestinal microecology and promote the health of the host.