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ABSTRACT Objective: To evaluate the expression of UCP1, UCP2, and UCP3 mRNA and encoded proteins in epicardial and mediastinal adipose tissues in patients with coronary artery disease (CAD). Subjects and methods: We studied 60 patients with CAD and 106 patients undergoing valve replacement surgery (controls). Expression levels of UCP1, UCP2, and UCP3 mRNA and encoded proteins were measured by quantitative real-time PCR and Western blot analysis, respectively. Results: We found increased UCP1, UCP2, and UCP3 mRNA levels in the epicardial adipose tissue in the CAD versus the control group, and higher UCP1 and UCP3 mRNA expression in the epicardial compared with the mediastinal tissue in the CAD group. There was also increased expression of UCP1 protein in the epicardial tissue and UCP2 protein in the mediastinum tissue in patients with CAD. Finally, UCP1 expression was associated with levels of fasting plasma glucose, and UCP3 expression was associated with levels of high-density lipoprotein cholesterol and low-density cholesterol in the epicardial tissue. Conclusions: Our study supports the hypothesis that higher mRNA expression by UCP genes in the epicardial adipose tissue could be a protective mechanism against the production of reactive oxygen species and may guard the myocardium against damage. Thus, UCP levels are essential to maintain the adaptive phase of cardiac injury in the presence of metabolic disorders.
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Objective:To evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in the renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats and its relationship with solute carrier family7 member11 (SLC7A11).Methods:SPF-grade healthy male Sprague-Dawley rats, aged 4 weeks, weighing 100-130 g, were fed with high-fat and high-sucrose diet freely.The weight of the rats was measured once a week.After the weight of the animals reached 240 g, 1% streptozotocin (STZ)-citrate buffer 35 mg/kg was injected intraperitoneally to induce type 2 diabetes mellitus.After injection of STZ, the animals were fed with high-fat and high-sucrose diet continuously.Blood samples were collected from the tail vein for determination of blood glucose concentrations 1 week later.When random blood glucose was ≥16.7 mmol/L for 3 times, the model of type 2 diabetes mellitus was considered to be established successfully.After the model was established successfully, the animals were fed with high-fat and high-sucrose diet continuously for 6 weeks.Eighteen rats with type 2 diabetes mellitus were selected and divided into 3 groups ( n=6 each) using a random number table method: diabetic sham operation group (group DS), diabetic myocardial I/R group (group DIR) and diabetic myocardial I/R+ HIF-1α agonist DMOG group (DIR+ DMOG group). Twelve non-diabetic rats were divided into 2 groups ( n=6 each) using a random number table method: non-diabetic sham operation group (NS group) and non-diabetic myocardial I/R group (NIR group). The rat myocardial I/R injury model was established by ligating the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion in anesthetized rats.Blood samples were collected from the right internal carotid artery at 120 min of reperfusion for determination of the serum creatinine (Cr), urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) concentrations (by enzyme-linked immunosorbent assay). Renal tissues were obtained for examination of the pathological changes (by HE staining method) and for determination of the expression of HIF-1α and SLC7A11 (by Western blot). The damage to the renal tubules was scored. Results:Compared with group NS, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased in group DS and group NIR, the expression of HIF-1α and SLC7A11 was down-regulated in group DS, and the expression of HIF-1α and SLC7A11 was up-regulated in group NIR ( P<0.05). Compared with group DS, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased, and the expression of HIF-1α and SLC7A11 was up-regulated in group DIR ( P<0.05). Compared with group NIR, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased, and the expression of HIF-1α and SLC7A11 was down-regulated in group DIR ( P<0.05). Compared with group DIR, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly decreased, and the expression of HIF-1α and SLC7A11 was up-regulated in group DIR+ DMOG ( P<0.05). Conclusion:HIF-1α is involved in the renal injury induced by myocardial I/R, which is related to regulation of the expression of SLC7A11 in rats.
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Background Researches showed that elevatory blood glucose level results in long-term damage of cells and tissue,or metabolic memory phenomenon,and manipulation of hyperglycemic memory is a good approach in the prevention of diabetic complications.However,its mechanism is not clear.It is speculated that the pathogenesis of diabetic retinopathy (DR) in diabetic patients may be associated to related mechanisms.Uncoupling proteins (UCPs) can decrease the production of reactive oxygen species (ROS),which may be related to DR.Objective This study was to explore the association between DR and the single nucleotide polymorphisms (SNPs) of UCP genes in Chinese Han population with type 2 diabetes.Methods A cross-sectional study was performed.This study was approved by Ethic Committee of Affiliated First Hospital of Shanghai Jiao Tong University and complied with Declaration of Helsinki,and written informed consent was obtained from each subject prior to any medical examination.One thousand eight hundreds and seventy-five patients with type 2 diabetes mellitus were enrolled in Xinjing district of Shanghai city by cluster sampling from November 2014 to January 2015.The demographic and medical baseline characteristics,ocular examination and laboratory tests were obtained and periphery blood of 2 ml was collected for extraction of DNA.Eight tag SNPs of UCP1,three tag SNPs of UCP2,and seven tag SNPs of UCP3 were selected as marker locus for the detection of genotype by Sequenom Mass ARRAY.Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry platform were used for genotyping.Hardy-Weinberg equilibrium (HWE) analysis,allele and genotype frequencies,haplotype analysis,and association tests for DR and SNPs were performed by SAS and SHEsis software.Results A total of 530 DR patients were checked out from 1 875 subjects with type 2 diabetes mellitus,with the detection rate of 28.27％.rs660339 locn of UCP2 gene and rs1626521,rs668514 locus of UCP3 gene appeared to have low detectable rates,and the secondary allele base frequency of rs632862 in UCP2 gene was ＜0.01 and rs15763 of UCP3 gene was unmatched with HWE,therefore,these locus analysis was not included.In 13 SNPs locus included in the analysis,only 2 SNPs of UCP1 gene were related to DR.Compared with the non-diabetic retinopathy (NDR) patients,the G allele frequency of rs10011540 was increased (P =0.03,OR =1.31,95 ％ confidence interval[CI] =1.03-1.67,and T allele frequency of rs3811787 was decreased (P=0.04,OR=0.86,95％ CI=0.75-0.99) in DR patients.Genotyping detection showed that the C/C and A/A frequencies of rs3811790 in UCP1 gene were significantly more and C/A frequency was less in DR patients than those in NDR patients (all at P＜0.01).The logistic regression analysis indicated an association of SNPs of rs10011540 and rs3811787 with DR independent from glucose and disease duration.Conclusions The SNPs of rs10011540 and rs3811787 locus in UCP1 gene are associated with DR in Chinese type 2 diabetes patients.
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AIM: To observe the relationship between UCP2 mRNA expression in white adipose tissue and diet-induced obesity in SR-A I/II gene knock-out(SR-AⅠ/Ⅱ-/-) mice.METHODS: Fluorescent quantitative RT-PCR was used to detect UCP2 mRNA expression in mice epididymal white adipose tissue.The cellular morphological changes were analyzed by using image analysis.Serum TG,TC and LDL-C concentrations were measured by enzymatic determination.RESULTS: After fed with high fat diet for 12 weeks,average body weight of SR-A I/II-/-mice was much higher than that of wild type(SR-A I/II+/+) control mice(P