Alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues in obese women.

BACKGROUND: Animal model studies suggest that change in the members of the suppressor of the cytokine signaling (SOCS) family (mainly SOCS1 and SOCS3) is linked to the pathogenesis of obesity-related metabolic disorders. Moreover, epigenetic modification is involved in the transcriptional regulation of the SOCS gene family. Here, we aimed to evaluate the mRNA expression as well as gene promoter methylation of SOCS1 and SOCS3 in subcutaneous adipose tissue (SAT) from obese women compared to normal-weight subjects. We also intend to identify the possible association of SOCS1 and SOCS3 transcript levels with metabolic parameters in the context of obesity. METHODS: This study was conducted on women with obesity (n = 24) [body mass index (BMI) ≥ 30 kg/m 2] and women with normal-weight (n = 22) (BMI < 25 kg/m 2). Transcript levels of SOCS1 and SOCS3 were evaluated by real-time PCR in SAT from all participants. After bisulfite treatment of DNA, methylation-specific PCR was used to assess the putative methylation of 10 CpG sites in the promoter of SOCS1 and 13 CpG sites in SOCS3 in SAT from women with obesity and normal weight. RESULTS: It was found that unlike SOCS3, which disclosed an elevating expression pattern, the expression level of SOCS1 was lower in the women with obesity as compared with their non-obese counterparts (P-value = 0.03 for SOCS1 transcript level and P-value = 0.011 for SOCS3 transcript level). As for the analysis of promoter methylation, it was found that SOCS1 and SOCS3 methylation were not significantly different between the individuals with obesity and normal weight (P-value = 0.45 and P-value = 0.89). Correlation analysis indicated that the transcript level of SOCS1 mRNA expression had an inverse correlation with BMI, hs-CRP levels, HOMA-IR, and insulin levels. However, the SOCS3 transcript level showed a positive correlation with BMI, waist-to-height ratio, waist circumference, hip circumference, hs-CRP, HOMA-IR, insulin, fasting blood glucose, and total cholesterol. Interestingly, HOMA-IR is the predictor of the transcript level of SOCS1 (ß = - 0.448, P-value = 0.003) and SOCS3 (ß = 0.465, P-value = 0.002) in SAT of all participants. CONCLUSIONS: Our findings point to alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues from women with obesity. Moreover, mRNA expression of SOCS1 and SOCS3 in SAT was associated with known obesity indices, insulin resistance, and hs-CRP, suggesting the contribution of SOCS1 and SOCS3 in the pathogenesis of obesity-related metabolic abnormalities. However, further studies are required to establish this concept.

The gene expression of long non-coding RNAs (lncRNAs): MEG3 and H19 in adipose tissues from obese women and its association with insulin resistance and obesity indices.

BACKGROUND: There is evidence regarding the role of two lncRNAs: MEG3 and H19 the pathomechanism of obesity and related disorders. Here, we aimed to evaluate the expression of MEG3 and H19 in visceral adipose tissues (VAT) and subcutaneous adipose tissues (SAT) of obese women (n = 18), as compared to normal-weight women (n = 17). Moreover, we sought to identify the association of expression of MEG3 and H19 in SAT and VAT with obesity parameters, insulin resistance, and the mRNA expression of possible target genes involved in adipogenesis and lipogenesis including peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). METHODS: Real-time PCR was performed to investigate the mRNA expression of the above-mentioned genes in VAT and SAT from all participants. RESULTS: The results showed lower mRNA levels of H19 in SAT of obese women, compared to normal-weight women, while MEG3 expression was significantly higher in the SAT of the obese group rather than controls. Correlation analysis indicated that the transcript level of H19 had an inverse correlation with obesity indices and HOMA-IR values. However, MEG3 expression displayed a positive correlation with all the indicated parameters in all participants. Interestingly, a positive correlation was found between transcript level of MEG3 in SAT with FAS and PPARγ. However, there was an inverse correlation between SAT expression of H19 and FAS. CONCLUSIONS: It appears that lncRNAs, MEG3 and H19, are involved in obesity-related conditions. However, more clinical studies are still required to clarify the relationships between lncRNAs with obesity and related abnormalities.

Emerging Role of miR-372 and miR-101a in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: microRNAs (miRNAs) have an important role in cancer development and progression. It has been shown that miR-372 and miR-101 are involved in cancer progression. In the present study we evaluated expressions of these miRNAs and their serum levels in patients with head and neck squamous cell carcinoma (HNSCC) and controls. METHODS: We conducted this case-control study on 60 patients with HNSCC and 30 controls. Patients were diagnosed by histological assessments of their tissues. Expressions of EGFR, PTEN, PI3K/CA, miR-372, and miR-101a were evaluated in the tissues, along with serum levels of the miRNAs. RESULTS: Tissue expression of PTEN decreased in HNSCC, and expressions of EGFR and PI3K increased in HNSCC tissues compared to the controls. Tissue expressions of miR-372 increased and miR-101a decreased in HNSCC tissues compared to the controls. We observed significantly lower serum levels of miR-101a in patients; however, these findings for miR-372 were not significant. A strong correlation existed between serum levels and tissue expression of miR-101a. Notably, miR-101a serum levels showed good sensitivity and specificity for diagnosis of HNSCC. CONCLUSIONS: The results showed that HNSCC patients had higher tissue expression of miR-372 and lower expression of miR-101a. Also, serum levels of miR-101a were lower in HNSCC patients. We observed that miR-101a had good sensitivity and specificity for diagnosis of HNSCC. The present study suggested that miR-101a could be a potential biomarker for HNSCC.

Clinical significance of long noncoding RNA VIM-AS1 and CTBP1-AS2 expression in type 2 diabetes.

BACKGROUND/AIMS: The risk of type 2 diabetes (T2D) is determined by a combination of genetic and environmental factors. Multiple studies have proposed that long noncoding RNAs (lncRNAs) are crucial molecules in regulating several biological processes and complex diseases. The study was aimed at investigating the association between the expression levels of lncRNA VIM-AS1, lncRNA CTBP1-AS2, and T2D susceptibility. METHODS: lncRNA VIM-AS1 and lncRNA CTBP1-AS2 in the peripheral blood mononuclear cell (PBMC) of 100 healthy individuals and 100 T2D patients were collected for Quantitative Real-Time RT-PCR analysis. A logistic regression was performed to understand whether the likelihood of T2D can be predicted based on the expression levels of lncRNA VIM-AS1 and lncRNA CTBP1-AS2. Receiver operating characteristic (ROC) analysis was also performed to determine the statistical analysis of VIM-AS1 and CTBP1-AS2 levels in 200 samples. RESULTS: Our results display that decreased levels of VIM-AS1 and CTBP1-AS2 in PBMC were associated with diabetes in Iranian population. The logistic regression revealed that Systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), Fasting blood glucose (FBG) and CTBP1-AS2 are substantial predictors of T2D. The ROC analysis of CTBP1-AS2 revealed the area under the ROC curve (AUC) of 0.68 with a sensitivity of 58.7% and specificity of 75.3% in distinguishing nondiabetic from diabetic subjects. The ROC analysis of VIM-AS1 determined AUC of 0.63 with a sensitivity of 56.1% and specificity of 68.37% in distinguishing the two diagnostic groups. CONCLUSION: lncRNA VIM-AS1 and lncRNA CTBP1-AS2 expression levels are associated with T2D susceptibility.

Circulating miR-625 as an Emerging Biomarker for Liver Cirrhosis.

BACKGROUND: Sensitive and specific diagnostic indicators are essential for liver cirrhosis. This study aims to analyze two plasma microRNAs (miR-625 and miR-920) as possible biomarkers for liver cirrhosis. METHODS: miR-625 and miR-920 expressions were analyzed in the plasma of 40 patients with liver cirrhosis and 41 healthy controls. Plasma levels of miR-625 and miR-920 were assessed by qRT-PCR. Analysis of the results was performed by the Mann-Whitney U-test. Spearman's test was used to show correlations between the miR-625 and clinical parameters. Receiver operating characteristic (ROC) analysis was performed to assess sensitivity and specificity. RESULTS: miR-625 is downregulated in patients with liver cirrhosis. Expression of miR-625 correlated with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. ROC curve analysis revealed that miR-625 had a sensitivity of 82.4% and specificity of 88.9% (area under the curve (AUC): 0.902) which indicated a high diagnostic power for cirrhosis. CONCLUSIONS: This study demonstrates for the first time that, miR-625 may be considered as a potential noninvasive biomarker for diagnosis of liver cirrhosis in patients, irrespective of etiology.

Deregulation of long noncoding RNA SNHG17 and TTC28-AS1 is associated with type 2 diabetes mellitus.

Long noncoding RNAs (lncRNAs) have emerged as key players in several biological processes and complex diseases including type 2 diabetes mellitus (T2DM). The purpose of this study was to investigate the expression levels of SNHG17 and TTC28-AS1 in T2DM patients. Quantitative real-time RT-PCR analysis was performed using peripheral blood mononuclear cells (PBMCs) samples from patients diagnosed with T2DM and healthy controls. Binary logistic regression analysis was carried out to determine the odds of development of T2DM based on expression levels of lncRNAs and clinical characteristic of the subjects. Spearman's correlation analysis was used to clarify the correlation between SNHG17 and TTC28-AS1 expressions to metabolic features. We found that SNHG17 and TTC28-AS1were down-regulated in the T2DM group compared to the healthy control group. The logistic regression revealed that body mass index (BMI), systolic blood pressure (SBP), fasting blood glucose (FBG) and TTC28-AS1 expression substantially affect T2DM susceptibility. Furthermore, expression of SNHG17 was negatively correlated with high-density lipoprotein cholesterol (HDL-C) and expression of TTC28-AS1 was positively correlated with low-density lipoprotein cholesterol (LDL-C). Decreased expressions of lncRNAs TTC28-AS1 and SNHG17 in T2DM are possibly associated with the development of T2DM.

Long non-coding RNA LY86-AS1 and HCG27_201 expression in type 2 diabetes mellitus.

Long non-coding RNAs (LncRNAs) are non-coding RNAs. The potential roles of lncRNAs in type 2 diabetes mellitus (T2DM) are not well-known. In this study, we aim to assess the expression levels of LY86-AS1 and HCG27_201 in T2DM patients and a healthy control group. We obtained whole blood and serum samples from 100 T2DM and 100 non-diabetic subjects. Peripheral blood mononuclear cells (PBMCs) were extracted from whole blood samples using Ficoll. Total RNA was isolated from PBMCs obtained from patients with type 2 diabetes mellitus and healthy control individuals using TRIzol LS reagent (GeneAll Biotechnology Co., LTD.). Extracted RNA was used to synthesize complementary DNA (cDNA) with a Reverse Transcription Kit (Takara). Real-time was performed with SYBR Green (Takara) and monitored by a Rotor-Gene (Qiagen) system. We performed quantitative PCR analysis of the LY86-AS1 and HCG27_201 lncRNA expression levels in the 200 samples. Here we found that the expression of LY86-AS1 and HCG27_201 were down regulated in the T2DM group compared with the control group. We further identify that the expression of both lncRNAs was negatively correlated with fasting blood sugar (FBS) levels. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of LY86-AS1 and HCG27_201 as biomarkers for T2DM. ROC analysis demonstrated that LY86-AS1 with an area under the ROC curve (AUC) of 0.747 (P < 0.0001, sensitivity: 64.6, and specificity: 79.8) might be the potential novel diagnostic biomarkers for T2DM. Lower expression of our two studied long non-coding RNAs LY86-AS1 and HCG27_201 in type 2 diabetes mellitus patients indicates their role in the pathogenesis of T2DM. Furthermore, LY86-AS1 could possibly be used as a diagnostic marker for T2DM.

Downregulation of long non-coding RNAs LINC00523 and LINC00994 in type 2 diabetes in an Iranian cohort.

Long non-coding RNAs (lncRNAs) are a subclass within the non-coding RNA repertoire that have potential roles in type 2 diabetes mellitus (T2DM). However, the biological function and molecular mechanisms of lncRNAs in T2DM remain largely unknown. The purpose of this study is to investigate the association between LINC00523 and LINC00994 expressions and T2DM susceptibility in an Iranian cohort. In this case-control study, we obtained whole blood and serum samples from 100 T2DM patients and 100 healthy subjects. We extracted peripheral blood mononuclear cells (PBMCs) from whole blood samples using Ficoll-Hypaque density-gradient centrifugation. Total RNA was extracted from the PBMC lysates by using the TRIzol-LS reagent (GeneAll). Finally, a quantitative real-time PCR (qPCR) assay was used to detect LINC00523 and LINC00994 lncRNA expression levels in the 200 samples. LINC00523 and LINC00994 expressions significantly decreased in patients with T2DM compared to the healthy participants, with a fold change for LINC00523 of 0.157 and 0.159 for LINC00994. We observed a significant inverse correlation between the expressions of these lncRNAs with FBS. Receiver operating characteristic (ROC) curve analysis revealed that LINC00523 has a higher area under the ROC curve (AUC) of 0.7430 and a lower P-value (P < 0.0001), in addition to a sensitivity of 81.44% and specificity of 61.11%. Therefore, LINC00523 could be considered a potential diagnostic biomarker for T2DM. Decreased expressions of LncRNAs LINC00523 and LINC00994 in T2DM is possibly associated with pathogenicity of T2DM in Iranian population. Moreover, LINC00523 can perhaps be considered as effective diagnostic biomarkers for T2DM.

Association of the rs1870634 Variant in Long Intergenic Non-protein Coding RNA 841 with Coronary Artery Disease: A GWAS-Replication Study in an Iranian Population.

Recent genome-wide association studies (GWAS) identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). Replication of GWAS findings in different population corroborated the observed association in the parent GWAS. In this study, we aimed to replicate the association of rs1870634, a GWAS identified SNP, to CAD in an Iranian population. The study population consisted of 267 subjects undergoing coronary angiography coronary angiography including 155 CAD patients and 112 non-CAD age- and gender-matched controls. The genotype determination of rs1870634 SNP performed using high-resolution melting analysis (HRM) technique. Our results revealed that the GG genotype frequency was significantly higher in CAD patients compared with controls (P = 0.03). The results of binary logistic regression suggested that this genotype was significantly associated with CAD risk adjustment for age, BMI, sex, TC, and LDL-C lipid levels (OR of 2.78, 95% CI (1.10-7.01), P = 0.03). Moreover, our results showed that the GG+TG genotypes were 2.52 times more likely to develop CAD (95% CI 1.05-6.03) than TT genotype carriers after adjusting for age, sex, and lipid profiles (P = 0.037). These data showed that the GG genotype could be associated with increased risk of CAD in a sample of Iranian population.

The Circulating Levels of Complement-C1q/TNF-Related Protein 13 (CTRP13) in Patients with Type 2 Diabetes and its Association with Insulin Resistance.

BACKGROUND: Complement-C1q/TNF-related protein 13 (CTRP13) is a novel adipokine involved in the regulation of energy metabolism. Here, we sought to evaluate serum levels of CTRP13 and adiponectin in patients with type 2 diabetes (T2D) (n = 40) and healthy subjects (n = 40) and also to study the association of CTRP13 levels with diabetes-related indices. METHODS: Circulating levels of CTRP13 and adiponectin were measured by enzyme-linked immunosorbent assay (ELISA) in T2D patients (n = 40) and in an age and gender-matched control group (n = 40). The anthropometric assessment and biochemical evaluation were done in all subjects. RESULTS: Circulating levels of CTRP13 and adiponectin were significantly lower in T2D patients in comparison with controls ( = 0.025 and p < 0.001, respectively). CTRP13 was inversely correlated with fasting blood sugar (Spearman's  = -0.420, p < 0.001), HbA1C (Spearman's  = -0.554, p < 0.001), and HOMA-IR (Spearman's  = -0.403, p < 0.001). ROC curve analysis showed that CTRP13 might be used as a biomarker for differentiating T2D patients from healthy individuals (area under the curve with 95% confidence intervals = 0.841, 0.752 - 0.929). A CTRP13 level equal to or lower than 0.885 ng/mL was found to be the optimal cutoff (sensitivity = 92.5%, specificity = 70%, Youden Index = 0.625) for differentiating T2D patients from healthy individuals. CONCLUSIONS: It appears that CTRP13 is a novel adipokine associated with T2D in humans as its serum level was significantly lower in T2D patients and also was inversely correlated with insulin resistance and FBS in humans.

The high-intensity interval training (HIIT) and curcumin supplementation can positively regulate the autophagy pathway in myocardial cells of STZ-induced diabetic rats.

OBJECTIVE: Targeting autophagy is a new therapeutic strategy for the complications of diabetes,such as diabetic cardiomyopathy (DCM). During diabetes, increased or insufficient autophagic activity causes aberrations in cellular homeostasis. Regarding the conflicting and unclear results regarding the effect of HIIT and curcumin supplementation on the expression of genes associated to autophagy, this study aimed to assess whether 4-week high-intensity interval training (HIIT) and curcumin supplementation are able to influence the expression of autophagy-related genes in myocardial cells of diabetic rats. METHODS: In an experimental design, 24 male Wistar rats were randomly divided into 4 groups: non-diabetic control (NC), diabetic control (DC), diabetes + HIIT (D + HIIT), and diabetes + curcumin (D + CU). After HIIT program and curcumin treatment, the genes expression of autophagy pathway were assessed in the myocardium by real-time PCR Tanique. RESULTS: The results indicated that the expression levels of ATG1, Beclin1, ATG5, and LAMP-2 genes were significantly reduced in the DC group compared to the NC group (p < 0.001). Following 4-week HIIT, the expression of Beclin1, ATG-5, and LAMP-2 improved considerably compared to the DC group (p < 0.001, p < 0.001, and p < 0.05, respectively). In addition, after 4 weeks of curcumin supplementation, the expression levels of ATG-5 and Beclin-1 were significantly improved compared to the DC group (p < 0.001, p < 0.05, respectively). It seems HIIT and curcumin supplementation can be an effective approach for inducing autophagy and improving cardiac function in DCM rats.However, HIIT seems more effective than curcumin in this regard.

Bacillus coagulans T4 and Lactobacillus paracasei TD3 Ameliorate Skeletal Muscle Oxidative Stress and Inflammation in High-Fat Diet-Fed C57BL/6J Mice.

Background: This study aims to investigate the effects of Bacillus coagulans T4 and Lactobacillus paracasei TD3 probiotics on skeletal muscle inflammation and oxidative stress in C57BL/6J mice fed a high-fat diet (HFD). Methods: Probiotics B. coagulans T4, and L. paracasei TD3 were administered to male C57BL/6J mice fed with HFD. The gene expression of macrophage infiltration markers, inflammatory cytokines, and oxidative stress indicators in the muscle tissue was investigated. Results: Treatment with B. coagulans T4 and L. paracasei TD3 reduced macrophage infiltration, accompanied by a decrease in the expression of monocyte chemoattractant protein-1 (MCP-1) and an increase in the expression of interleukin (IL)-10. On the other hand, L. paracasei TD3 decreased malondialdehyde (MDA) while B. coagulans T4 decreased carbonyl and increased catalase activity. Conclusions: Treatment with probiotics B. coagulans T4 and L. paracasei TD3 partially ameliorated obesity-induced skeletal muscle inflammation in HFD-fed mice.

Association between HDACs and pro-inflammatory cytokine gene expressions in obesity.

Histone deacetylases (HDACs) are important players in a variety of physiological and pathological conditions. Few studies have addressed HDAC expressions in human adipose tissue in obese individuals, and their association with pro-inflammatory cytokines. Here, we compared 20 non-obese and 20 obese women to investigate possible changes in gene expressions of HDAC2, 4, 5, and 6 in the subcutaneous adipose tissues (SAT) and visceral adipose tissues (VAT) of these individuals. Our findings showed decreased HDAC5 expression in SAT and elevated HDAC4 expression in VAT from the obese group compared with the non-obese group. Our analyses showed negative correlations between HDAC2, 5, and 6 and the obesity indices and positive correlations between HDAC4 and obesity indices. HDAC2 showed a positive correlation with pro-inflammatory cytokines whereas HDAC4, 5, and 6 were negatively correlated with pro-inflammatory cytokines. Our findings provide new evidence that implicates the important roles of HDACs in obesity and obesity-associated inflammation.

Association of rs2954029 and rs6982502 Variants with Coronary Artery Disease by HRM Technique: A GWAS Replication Study in an Iranian Population.

Background: Genome-wide association studies (GWAS) have been the primary tool for an unbiased study of the genetic background of coronary artery disease (CAD). They have identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). In this study, we aimed to replicate the association of rs2954029 and rs6982502, a GWAS identified SNP, to CAD in an Iranian population. Methods: A sample of 285 subjects undergoing coronary angiography, including 134 CAD patients and 151 healthy. The genotype determination of rs2954029 and rs6982502 SNPs performed using the high-resolution melting analysis (HRM) technique. Results: Our results revealed that the TT genotype of rs2954029 (p= 0.009) and rs6982502 (p< 0.001) were significantly higher in CAD patients compared with controls. Binary logistic regression showed that rs6982502 and rs2954029 increase the risk of CAD incidence (2.470 times, p= 0.011, 95% CI= [1.219-4.751], and 2.174 times, p= 0.033, 95% CI= [1.066-4.433] respectively). After adjusting for confounders, we found that rs6982502 and rs2954029 are significantly associated with CAD risk. Conclusion: These data showed that the TT genotype of rs2954029 and rs6982502 is associated with the risk of CAD in a hospital-based sample of the Iranian population, which has replicated the result of recent GWAS studies.

Low level of adiponectin predicts the development of Nonalcoholic fatty liver disease: is it irrespective to visceral adiposity index, visceral adipose tissue thickness and other obesity indices?

We aimed to study the correlation of adiponectin level with insulin resistance (IR), carotid intima-media thickness (cIMT), and various obesity indices especially visceral adipose tissue (VAT) thickness, and visceral adiposity index (VAI), in patients with NAFLD (n = 41), T2D (n = 22), NAFLD + T2D (n = 41), and healthy subjects (n = 20). Results showed the median level of adiponectin in patients with NAFLD (2.97 µg/mL) and ones with NAFLD + T2D (3.21 µg/mL) is significantly lower rather than in controls (4.39 µg/mL). Moreover, VAI is the only predictor for adiponectin concentration in the combination of patient groups and also in all participants independent of IR and other obesity indices. Adiponectin level had also a positive correlation with cIMT and IR in NAFLD patients. Interestingly, lower level of adiponectin was associated with the presence of T2D, NAFLD, and NAFLD + T2D independent of IR and obesity indices. Collectively, it seems that VAI reflecting visceral adipose tissue function is a possible predictor of adiponectin level.

The circulating levels of CTRP1 and CTRP5 are associated with obesity indices and carotid intima-media thickness (cIMT) value in patients with type 2 diabetes: a preliminary study.

BACKGROUND: There is growing evidence that the C1qTNF-related protein (CTRP) family has a crucial role in the pathophysiology of metabolic disorders such as type 2 diabetes (T2D) and obesity. We sought to identify the association of CTRP1 and CTRP5 circulating levels with various obesity parameters such as visceral adipose tissue (VAT) thickness, visceral adiposity index (VAI), and with carotid intima-media thickness (cIMT) in patients with T2D and controls. METHODS: This preliminary study consisted of men with T2D (n = 42) and men without T2D (n = 42). The measurement of cIMT and VAT thickness was performed using an Accuvix XQ ultrasound. Circulating levels of CTRP1, CTRP5, and adiponectin were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: CTRP-1 and CTRP1/CTRP5 ratio were markedly higher in patients with T2D compared to controls (p < 0001 and p = 0004 respectively). Interestingly, binominal logistic regression revealed that a higher circulating level of CTRP1 was associated with the presence of T2D (odds ratio [OR]: 1.009 [95% CI: 1.004-1.015]; P = .001). CTRP1 circulating levels were correlated with WHR, VAT, and HOMA-IR in the whole population study. Also, we observed that the ratio of CTRP1 to CTRP5 in plasma (ß = 0.648, P = 0.005) and CTRP5 circulating levels (ß = 0.444, P = 0.049) are independently associated with cIMT value. CONCLUSIONS: Our results indicated that CTRP1 and CTRP5 concentrations were correlated with atherosclerosis in men with T2D and these adipokines might have a causal role for cardiometabolic risk in T2D.However, more studies in large sample sizes are required to clarify the role of CTRPs in T2D pathogenesis.

In vitro inhibition of low density lipoprotein carbamylation by vitamins, as an ameliorating atherosclerotic risk in uremic patients.

INTRODUCTION: Previous studies have shown that the increase of carbamylated LDL (cLDL), a product of nonenzymatic modification of LDL in human serum by urea-derived cyanate, may cause cardiovascular complications in patients with chronic renal insufficiency. This study examined the inhibitory effect of ascorbic acid, alpha-tocopherol and lycopene on LDL carbamylation in an in vitro model system. METHODS: After isolation of LDL from plasma using an ultracentrifuge technique, cyanate was added to it and then LDL carbamylation was measured in both the absence and presence of ascorbic acid, alpha-tocopherol and/or lycopene by the colorimetric method at 530 nm. RESULTS: The findings indicated that these vitamins inhibit LDL carbamylation and the most effective vitamin of the three is lycopene. Moreover, the effect of lycopene on this process increased in the presence of ascorbic acid and alpha-tocopherol. CONCLUSION: This study indicated that ascorbic acid, alpha-tocopherol and lycopene with antioxidant activity can probably inhibit LDL carbamylation and therefore may have a role in ameliorating atherosclerotic risk of patients with kidney failure. However in vitro and in vivo investigations are required to confirm the exact effects of these vitamins on patients suffering from uremic disorders.

Increased mRNA Expression of CTRP3 and CTRP9 in Adipose Tissue from Obese Women: Is it Linked to Obesity-Related Parameters and mRNA Expression of Inflammatory Cytokines?

BACKGROUND: Obesity, a medical condition with impaired adipokine secretion and function, has a detrimental effect on insulin and glucose metabolism. CTRP3 and CTRP9 are adipokines with possible roles in energy homeostasis regulation. We sought to compare CTRP3, CTRP9, and inflammatory gene expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery and non-obese women as controls. METHODS: For this study, the investigators recruited 20 morbidly obese women (BMI> 35) who qualified for bariatric surgery and 20 normal-weight women (BMI< 25) who underwent elective surgeries. Real-time PCR was performed to investigate mRNA expression of CTRP3, CTRP9, and the inflammatory genes IL1-ß, IL-6, MCP-1, and TNF-α in SAT and VAT from both obese patients and controls. RESULTS: We observed that CTRP3 mRNA levels were significantly greater in VAT from obese patients than from controls (P< 0.0003). Also, patient group had higher levels of CTRP9 that control group (P< 0.0026). Inflammatory cytokines were markedly increased in SAT of obese patients compared to controls (P< 0.05). In addition, our results revealed a positive correlation of CTRP9 with HOMA-IR and waist circumference in VAT and CTRP3 with IL-1ß, MCP-1, and TNF-α in SAT. CONCLUSION: Both CTRP3 and CTRP9 expression were significantly higher in VAT from obese patients than from controls, and CTRP3 expression positively correlated with inflammatory parameters. Our findings indicate that CTRP3 and CTRP9 might be important in regulating glucose metabolism and obesity-related conditions such as inflammation.

The C1q/TNF-related proteins (CTRPs) in pathogenesis of obesity-related metabolic disorders: Focus on type 2 diabetes and cardiovascular diseases.

The growing evidence has been tried to explain and characterize C1q/TNF- related proteins (CTRPs) family as the potential diagnostic or therapeutic targets of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes (T2D), and cardiovascular disorders. However, the underlying mechanism is still obscure. Unraveling the signaling pathways downstream of CTRP family members is of great interest and could certainly be beneficial for finding new insights into therapeutic strategies for improving metabolic abnormalities. This review focused on the role of CTRP members in the initiation and development of obesity-related metabolic disorders with a focus on T2D and cardiovascular diseases. Here we summarize and discuss the role of CTRPs in the regulation of insulin signaling, inflammatory pathways, and energy metabolism, and other signaling pathways pertinent to the pathogenesis of T2D and cardiovascular diseases. We also review available clinical studies to better elucidate the roles of these potential molecules in the initiation and development of the afore-mentioned disorders.

High-intensity interval training (HIIT) alleviated NAFLD feature via miR-122 induction in liver of high-fat high-fructose diet induced diabetic rats.

Background: Exercise intervention is strongly recommended to manage metabolic diseases. In this study, we investigate, whether HIIT and CET can induce hepatic miR-122 expression, NAFLD rats with diabetes.Methods: 40 Wistar rats divided into 2 groups, non-diabetic (NDC) and diabetic .Type 2 diabetes was induced by high-fat high-fructose diet (HFHFD). Then diabetic rats were subdivided into three groups: diabetic control (HFHFD + DC), CET (HFHFD + CET), and HIIT (HFHFD + HIIT). After eight weeks of exercise on a rodent treadmill, we measured miR-122 and its target genes expression in the liver of rats.Results: HIIT decreased the expression of FAS, ACC, SREBP-1c compared with HFHFD + DC (p = .004, p = .032, p = .043, respectively), and could partially increase miR-122 expression as compared with HFHFD + DC (26.8%, p = .68).Conclusions: Exercise training could be a non-pharmacological intervention for improvement of NAFLD of diabetic rats by induction of miR-122. HIIT had a greater effect on NAFLD amelioration than CET.