The Correlation Study Between Autophagy Indicators ATG7,Beclin1 And NAFLD

Objective: Non-alcoholic fatty liver disease(NAFLD)is characterized by lipid accumulation within hepatocytes and may progress to non-alcoholic steatohepatitis(NASH)even hepatic cirrhosis.Although the pathological mechanism of NAFLD hasn’t been fully understood,many studies suggested that metabolic stress,inflammation,endoplasmic reticulum stress and autophagy were all involved.Autophagy is a major intracellular degradative process and is required for homeostasis of biomacromolecules.Once the autophagy balance is disrupted,it can cause many diseases,including type 2 diabetes(T2DM),NAFLD,cardiovascular disease and cancer etc.Recently,many studies suggested that autophagy is important in the regulation of lipid metabolism and may play a role in the pathogenesis of NAFLD.However,the research of the association between autophagy and NAFLD in vivo is rare and the results of study in vivo and in vitro are inconsistent.Therefore,in this study,we evaluated the correlation between autophagy and NAFLD by measuring serum autophagy indicators Autophagy related gene 7(ATG7),Beclin1 level in patients with NAFLD.Methods: This study was conducted in Health Examination Center of Hebei Province General Hospital from January to April,2015.A total of 176 individuals were involved in the study.Written informed consent was obtained from them.Oral glucose tolerance test with a 75 g of glucose load was proceeded in all subjects and their eripheral venous blood samples were collected.Serum was obtained by centrifugation at 3,000 rpm for 10 min.Blood glucose,blood lipids and other parameters were analysed by automatic biochemical analyzer.Glycated hemoglobin was detected by high performance liquid chromatography.Serum insulin,thyroid hormones and thyroid stimulating hormone were detected by electrochemical luminescence method.The homeostasis model assessment of insulin resistance(HOMA-IR)was used to evaluate IR,as calculated by the following formula: Fasting glucose(mmol/L)×fasting insulin(mU/L)/22.5.ATG7 and Beclin1 serum levels were measured by enzyme-linked immunosorbem assay.All statistical analyses were performed using SPSS 21.0 software.A P-value <0.05 was regarded as statistically significant.Results:1 The comparison of the baseline clinical characteristicsWe observed the differences of age,BMI,glucose,lipid levels and other values between control group and NAFLD group.There was no significant difference in age,TC and thyroid hormones between NAFLD group and control group(P>0.05).Compared with control group,the NAFLD group had higher BMI and WHR(P<0.05).The NAFLD group also had higher levels of serum TG,FINSand 2h INS than control group(P<0.05).Compared with the control group,the levels of HDL-C and APOA1 were lower in the NAFLD group(P<0.05).Furthermore,the NAFLD group had increased HOMA-IR than control group(P=0.001).We observed the differences of serum levels of total triiodothyronine(T3),total thyroxine(T4)and thyroid stimulating hormone(TSH)between control group and NAFLD group.Compared with control group,the levels of T3 and T4 were higher in NAFLD group.And the level of TSH in NAFLD group was lower than control group.However,there were no significant difference between the two groups(P>0.05).2 Comparison of serum levels of Atg7 and Beclin1Compared with control group,the serum level of Atg7 was higher in NAFLD group,and the difference was statistically significant(P<0.05).Although serum Beclin1 level in NAFLD group was higher than in control group,there were no significant difference between the two groups(P>0.05).3 Associations between serum total Atg7 level and metabolic risk factorsThe correlation of serum Atg7 level with related metabolic factors was detected by Spearman’s correlation coefficient.The results showed that serum Atg7 level was positively correlated with BMI,LDL-C,FINS and HOMR-IR(P<0.05).4 Associations between serum total Beclin1 level and metabolic risk factorsThe correlation of serum Beclin1 level with related metabolic factors was detected by Spearman’s correlation coefficient.The results showed that serum Beclin1 level was positively correlated with BMI and TG(P<0.05).5 The correlation of NAFLD with related metabolic factorsIn the study,NAFLD was treated as an independent factor.We detected the correlation of NAFLD with serum levels of Atg7 and Beclin1,age,sex,BMI,WHR,lipid,HBA1 c by multivariable logistic regression.The results indicated that there was a positive association between NAFLD and BMI,TG,HOMR-IR and Atg7(P<0.001).Conclusion:1 Compared with control group,the levels of ATG7 and Beclin1 were higher in NAFLD group.Although serum Beclin1 level in NAFLD group was higher than in control group,there were no significant difference between the two groups)2 Serum Atg7 was positively correlated with BMI,LDL-C,FINS and HOMR-IR,and serum Beclin1 level was positively correlated with BMI and TG.3 Increase of autophagy indicators ATG7 level was positively associated with NAFLD,which was a risk factor of NAFLD.Therefore,the results indicated autophagy may play a role in the pathogenesis of NAFLD.