Relationship Between The MRNA Expression Of Adipose Triglyceride Lipase In Peripheral Blood Mononuclearcelis And Metabolic Syndrome

Background:Metabolic syndrome is a pathophysiological state composed by interrelated metabolic performance,including obesity,hypertension,dyslipidemia and hypergly cemia.Since its found, more and more attentions are being paid, because of some risk factors on arteriosclerosis, which can damage the target organs such as heart,brain and kidney. Its mechanism is still not entirely clear,except obesity and insulin resistance.Factors influencing the occurrence and development of metabolic are paid more attentions. A variety of factors have been found having a clear impact on it,including CRP,leptin,visfatin,adiponectin,peroxisome proliferator-activated receptor-8,adipose triglyceride lipase(ATGL).Since its found,adipose triglyceride lipase is more and more popular. ATGL plays an important role in regulating lipolysis,especially in adipose tissue.ATGL is mainly expressed in fat cells and testes, skeletal muscle,cardiac tissue,low secretion in the brain, lungs, and other organs.ATGL catalyzes the first step in adipocyte and muscle triglyceride hydrolysis,mainly to provide a substrate for subsequent hydrolysis,not involved in the metabolism of cholesterol and retinol.It has proved that ATGL knockout mice showed increased glucose tolerance, higher glucose utilization, liver than before, lower oxygen uptake, more sensitive to insulin response.It indicates tha ATGL may be involved in the produce and development of metabolic syndrome..Because carotid ultrasound monitoring is more sensitive, reproducible, no trauma, operability, low prices,now it is widely used in evaluating the severity of atherosclerosis,with high diagnostic value.Carotid arteries which are easy to find as the window surface of the body, has become the middle end point of large-scale clinical trials. Objective:(1)To investigate the mRNA expression levels of ATLG in peripheral blood mononuclear cells in patients with MS,and to probe into the potential mechanism underlying these changes.(2)To investigate the alterations in structure and function of the carotid artery,as well as the association of ATLG mRNA expression levels with these changes.Methods:According to IDF2005criteria of MS,we enrolled56patients with MS(26females and30males,54.97±9.98yr of age)and55people matched with age and sex (P>0.05) without MS(29females and26males,51.74±9.65yr of age).Height(H), weight (W),systolic blood pressure(SBP),diastolic blood pressure(DBP),waist circumference (WC) and hip circumference(HC).Pulse pressure(PP),body mass index(BMI)and waist—hip ratio(WHR)were calculated.Furthermore,fasting blood sample Was colle-cted from each subjects after12-14hours fast to determine the total cholesterol (TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and uric acid(UA),fasting blood glucose(FBG), insulin(FINS)and HOMA-IR.Briefly,PBMCs were isolated.TOtal RNA was extracted using Trizol one—step method.The RT-PCR technique was applied to detect the mRNA expressions of ATLG in PBMCs.B-mode ultrasonography of the carotid arteries was performed and Ultrasound images were acquired using a5～10MHz linear array transducer and a commercially available ultrasound machine(Vivid7dimension;General Electric Medical Systems,Horten,Norway).ECG data were recorded concurrently.carotid ultrasonic parameters,including lumen diameter(D), intima-media thickness(IMT),plaque index,flow velocity(V),pressure-strain elastic modulus(Ep),normalized Ep,arterial stiffness(p),arterial compliance(AC),resistance index(D)and pulse index(PI),were measured.Echocardiograms were obtained with a commercially available ultrasoundmachine(Vivid7;GE Vingemed Ultrasound, Horten, Norway)with a1-to3-MHZ phased array transducer.The M-mode echocardiography, two-dimensionalechocardiography,pulsed-Doppler echocardiography and tissue Dopplerechocardiography were perfor-med respectively.All statistical analyses were performed using the SPSS19.0statistical program. Normally distributed data were expressed as means±SD or±SEM as indicated,and non-normally distributed data are presented as medians(quartile range).Continuous variables were compared between groups by unpaired Student’s t test.The associations between categorical ones was analyzed using the chi-square test.Correlation coefficients between the variables were determined using the Pearson’s method,meanwhile multiple regression analysis was performed to determine relationships between variables of interest.A P value<0.05was considered statisti-cally significant.Results:(1)Comparison of clinical and biochemical characteristics of the subjectsThere were no significant differences in age and gender between MS group and control group.Compared with the controls,the MS group showed significantly higher WHR,BMI, LDL,TG,TC,BP,FBG,ISI,but lower HDL-C(P<0.001, respectively).(2)Comparison of carotid ultrasonic parametersThe Dd(P<0.05), Ds(P<0.05) of the MS group were significantly higher than those of the control group. Furthermore the MS group showed significantly higher in The mean IMT(P<0.001), Ep(P<0.001),β(P<0.001)。(3)Comparison of gene expression parametersThe mRNA expression levels ofATGL [(7.04±3.66) vs (2.25±1.69)(P<0.001)], in PBMCs ofthe MS group weresignificantly higher than those of the control group.(4) Correlation of ATGL-mRNA expression levels with clinical and biochemical characteristics, and correlation between these two expression levelsATGL-mRNA expression level Was significantly correlated positively with age (r=0.405,P<0.001), SBP (r=0.428, P<0.001)、DBP (r=0.423, P<0.001), BMI (r=0.432, P<0.001)、TG (r=0.369, P<0.001)、HOMA-IR (r=0.403, P<0.001), and negatively with HDL-C (r=-0.252, P= 0.015).Multiple regression analysis showwing, age (β=0.292, P=0.004), TG (β=0.286, P=0.004) and HOMA-IR (β=0.251, P=0.009) were independent risk factors for the ATGL-mRNA expression increasion。(5) Correlation of ATGL-mRNA expression levels with carotid ultra-sonic para-metersATGL-mRNA expression level Was significantly correlated positively with IMT (r=0.398, P<0.001), Ep (r=0.379, P<0.001), β (r=0.317, P=0.003) Increased TG and ATGL-mRNA were independent risk factors for thickened IMT。 TG (β=0.268, P=0.010) and ATGL mRNA (β=0.210, P=0.024)Conclusions:(1) The mRNA expression levels of ATGL in PBMCs of the MS group were significantly increased. With regard to these changes, aging, elevated TG and HOMA-IRwere independent risk factors for the ATGL-mRNA expression reduction.(2) Significant alterations to carotid arteries of the MS patients include thickened IMT, increased plaque index, distended vessel diameter, reduced elasticity and augmented stiffness. The increased mRNA expression levels ofATGLin PBMCs were independent risk factors for the IMT thickening in MS.which indicated that1ATGL expression increasion may play an significant role in the development of early atherosclerosis lesions.