| Background and Aims:In recent years,the incidence of non-alcoholic fatty liver disease(NAFLD)in the world is increasing with the improvement of people’s living standards.Studies have shown that NAFLD is closely related to the occurrence and development of obesity,diabetes and hypertension and other chronic diseases.The huge threat that to human health and quality of life is obvious.However,the exact pathogenesis of NAFLD remains unclear and the treatment is extremely limited.Therefore,it is vital to clarify the etiology and early prevention of NAFLD.Helicobacter pylori(Hp),a gram-negative micro-aerobic bacteria,the global population infection rate is extremely high.Being one of the most common infectious pathogens in human body,it has been recognized as the important environmental pathogenic factor in chronic gastritis,digestive ulcers,gastric mucosa-associated lymphoid tissue(MALT)lymphoma and gastric cancer and other gastrointestinal diseases.And now,more and more clinical data show that Hp infection may also be associated with a variety of extra-gastric diseases,including blood system disease,cardiovascular disease and metabolic disease.Recently,many studies have reported that Hp infection is linked to NAFLD.NAFLD is one manifestation of metabolic syndrome(MS)in the liver and insulin resistance(IR)-mediated fatty ectopic deposition in the liver is the central part of its pathogenesis.A large number of studies have confirmed that Hp infection plays an important role in IR.Therefore,whether the persistent infection of Hp will eventually trigger NAFLD? Wherther the high fat diet,an important environmental factor of NAFLD,and Hp infection have a synergistic effect to the development of NAFLD? If it would lead to the occurrence of NAFLD,what is the possible pathogenesis? This series of problems need to be further studied.Materials and Methods:1.Hp strains(SS1,NCTC11637)infected C57BL/6 mice models were established.Both Hp infected groups and the control group were fed either a chow diet(CD)or high-fat diet(HFD).2.The body weight,energy utilization and blood biochemical indexes were measured after different dietary interventions 24 weeks.The levels of total cholesterol(T-CHOL),triglyceride(TG),low-density lipoprotein(LDL-C),and liver function transaminases including aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were tested using automatic biochemical analyzer.3.Animals were sacrificed after different dietary interventions 24 weeks.Liver tissues were separated and weighed.Histopathologic changes of liver tissue were observed by HE staining,and the severity of the liver fatty degeneration and inflammation were scored by NAS scoring system.The amount of triglyceride in liver tissue was quantitatively detected by triglyceride kit.4.The expression of IRS/PI3K/Akt signaling pathway in the liver tissue was detected by Western blot.The mRNA levels of lipid synthesis related enzymes including PPARγ,FASN,SREBP1 in the liver tissue were detected by Real-time PCR.Results:1.The effects of Hp infection on body weight and blood biochemical indicators in C57BL/6 mice after different dietary intervention.(1)In high-fat diet group,the body weight of C57BC/L mice was significantly higher than that in chow diet group(p <0.01).There was no significant difference between Hp infection group and non-infected group(p> 0.05).(2)The plasma LDL-C in the high-fat diet group was significantly higher than that in the chow diet group(p <0.01).In the high-fat diet groups,the plasma LDL-C of the HpSS1 infection group was significantly higher than that of the non-infected group(p<0.01).But there was no significant difference between the Hp infected group and the non-infected group(p> 0.05).(3)The plasma T-CHOL of the high-fat diet group was significantly higher than that of the chow diet group(p<0.01),but there was no significant difference between the Hp infected group and the non-infected group(p > 0.05).There was no significant difference of the plasma TG whether between the high-fat diet group and the chow diet group or between Hp infected groups and non-infected group(p > 0.05).(4)In the high-fat diet groups,serum ALT of the HpSS1 infected group was significantly higher than of the non-infected group.But in the chow diet groups,there were no significantly difference between the Hp infected group and the non-infected group(p> 0.05).There was no significant difference of the serum AST between the high-fat diet group and the chow diet group(p> 0.05).And there was no significant difference of the serum AST between the Hp infected group and the non-infected group(p>0.05).2.The effects of Hp infection on liver fat content in C57BL/6 mice after different dietary intervention.(1)There was no significant difference of the liver weight between the high-fat diet group and the chow diet group(p> 0.05).And there was no significant difference of the liver weight between the Hp infected group and the non-infected group(p>0.05).(2)The HE staining of liver tissues showed diffuse distribution of lipid droplets and fatty degeneration in the high-fat diet group,but there was no obvious fatty degeneration in the chow diet group.And in the high-fat diet groups,the liver steatosis of the HpSS1 infected group was more serious than that of the non-infected group.The NAS scores also have significant differences(p <0.01).(3)The oil red O staining of the liver tissues showed the lipid drops were more obvious in the high-fat diet group than those in the chow diet group.In the high-fat diet groups,the lipid drops of the HpSS1 infected group were also more obvious than that of the non-infected group.(4)The contents of triglyceride of the liver tissues were significantly higher in the high-fat diet group than that in the chow diet group(p<0.01).And in the high-fat diet groups,those were significantly higher in the HpSS1 infected group than those in the non-infected group(p<0.05).But,in the chow diet groups,there were no significant differences between the Hp infected group and the non-infected group(p> 0.05).3.The effects of Hp infection on the protein expression levels of IRS-1/PI3K/Akt signaling pathway and the mRNA expression levels of the key enzymes of lipid metabolism in the liver tissues.(1)The expression of p-Akt(Ser473)of the HpSS1 infected subgroup or the high-fat diet subgroup was not significantly different from that in the control subgroup in the liver tissue(p>0.05),while in the high fat diet groups,the HpSS1 infected subgroup was down regulation than the control subgroup(p<0.01).(2)In the the high-fat diet group or HpSS1 infected subgroup,the expression of IRS1 was not significantly different from that in the control subgroup(p>0.05),and there was no significant difference between the HpSS1 infected subgroup of the high-fat diet group and the control subgroup(p> 0.05)(3)The expression of p-IRS1(Tyr896)of the HpSS1 infected subgroup or the high-fat diet subgroup was not significantly different from that in the control subgroup in liver tissues(p>0.05),while It was significantly lower in the subgroup of the HpSS1 infected subgroup of the high-fat diet groups than that in the control subgroup(p <0.01).(4)The expression levels of PPARγ、SREBP1 and FASN mRNA in the high-fat diet groups were not significantly different from those in the chow diet group(p> 0.05),while the expression level of PPARγ mRNA in the Hp infected subgroup of the high-fat diet groups was higher than that in the control subgroup in the liver tissues(p <0.01).There was increasing trend of the expression levels of SREBP1 and FASN mRNA in the Hp infection subgroup than that in the control subgroup in the high fat diet groups.Conclusions:1.In the long-term high-fat diet condition,Hp infection may further aggravate NAFLD.2.The Hp infection in the long-term high-fat diet promoting the progress of NAFLD is related to the inhibition of the IRS-1/PI3K/Akt signaling pathway. |
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