Adiponectin Gene Research Articles

Body Fat Distribution, Adipocytokines Levels and Variability in Associated Genes and Kidney Transplant Outcomes.

Introduction: Body fat distribution is known to contribute to a variety of pathologies. Research Questions: We aimed to assess whether this distribution is associated with clinical outcomes in renal transplant recipients (RTR) and to examine its relationship with leptin and adiponectin gene variants and plasma concentrations. Design: Bioelectrical impedance analyses were performed in 236 RTR. Leptin/adiponectin levels were measured by immunoassay and relevant polymorphisms in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes were identified. Associations were assessed by logistic regression modeling. Results: The waist-to-height ratio (WHr) displayed a significant association with delayed graft function, acute rejection and post-transplant diabetes mellitus, with OR values of 2.04 (1.02-4.08) p = 0.045; 3.08 (1.22-7.79) p = 0.017 and 2.79 (1.16-6.74) p = 0.022, respectively. Waist circumference was linked to delayed graft function [OR = 1.03 (1.01-1.05), p = 0.025] and AR [OR = 1.041 (1.01-1.07), p = 0.009]. Leptin levels were significantly higher in patients who experienced rejection [19.91 ± 23.72 versus 11.22 ± 16.42 ng/ml; OR = 1.021 (1.01-1.04), p = 0.017]. The ADIPOQ rs1501299TT genotype showed a significant association with higher WHr (0.63 ± 0.11 vs 0.59 ± 0.87 for GG/GT genotypes; p = 0.015) and WC values (102.3 ± 14.12 vs 96.38 ± 14.65 for GG/GT genotypes; p = 0.021). Conclusion: WC, and especially WHr, are associated with adverse outcomes in renal transplantation and are affected by variability in the ADIPOQ gene.

Is Single Nucleotide Polymorphism ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) Associated With Uterine Leiomyomas? A Pilot Study.

Objective: Although polymorphisms of adiponectin gene (ADIPOQ) in obesity-related conditions have been the target of research efforts, little is known about this genetic marker in uterine leiomyomas. The aim of this pilot study was to analyze the frequencies of alleles and genotypes of Single Nucleotide Polymorphism ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) and to correlate it with the risk of uterine fibroids. Study Design: The Test Group comprised 90 women treated surgically for uterine leiomyomas in the Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, Polish Mother’s Memorial Hospital-Research Institute. 90 disease-free individuals were used as Controls. Patients within both groups were additionally stratified into lean, overweight and obese, according to Body Mass Index. Statistical analysis was performed between the two major groups and, furthermore, within the abovementioned subgroups. Results: The study revealed no statistically significant differences in the distribution of alleles and genotypes of SNP ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) between the two main groups. A weak correlation within distributions of alleles was observed between obese Test Patients and lean Controls. Conclusion: This pilot study has revealed no association between SNP ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) and uterine fibroids. Further studies on larger groups are warranted to elucidate whether this SNP may be correlated with uterine leiomyomas.

Combined training increases thermogenic fat activity in patients with overweight and type 2 diabetes.

Exercise is an important strategy in the management of diabetes. Experimental studies have shown that exercise acts, at least in part, by inducing the production of myokines that improve metabolic control and activate brown/beige adipose tissue depots. Combined training (CT) is recommended by the major diabetes guidelines due to its metabolic and cardiovascular benefits, however, its impact on brown/beige adipose tissue activities has never been tested in humans with overweight and type 2 diabetes (T2D). Here, we evaluated the effects of 16-week combined training (CT) program on brown adipose tissue activity; browning and autophagy markers, and serum pro-thermogenic/inflammatory inducers in patients with overweight and T2D. Thirty-four patients with overweight and T2D were assigned to either a control group (CG) or a combined training group (CTG) in a randomized and controlled study. Functional/fitness parameters, anthropometry/body composition parameters, blood hormone/biochemical parameters, thermogenic/autophagic gene expression in subcutaneous adipose tissue were evaluated before and at the end of the intervention. In addition, cold-induced 18-Fluoroxyglucose Positron Emission Computed Tomography (18F-FDG PET/CT) was performed in the training group before and after the end of the intervention. CT increased cervical/supraclavicular brown adipose tissue (BAT) thermogenic activity (p = 0.03) as well as in perirenal adipose tissue (p = 0.02). In addition, CT increased the expression of genes related to thermogenic profile (TMEM26: + 95%, p = 0.04; and EPSTI1: + 26%, p = 0.03) and decreased autophagic genes (ULK1: -15%, p = 0.04; LC3: -5%, p = 0.02; and ATG4: -22%, p < 0.001) in subcutaneous adipose tissue. There were positive correlations between Δ% BAT activity with Δ% of post training energy expenditure cold exposure, HDL-c, IL4, adiponectin, irisin, meteorin-like, and TMEM26 and ZIC1 genes, besides negative correlations with LDL-c, total cholesterol and C-reactive protein. This is the first evidence of the beneficial actions of CT on adipose tissue thermogenic activity in humans, and it adds important support for the recommendation of CT as a strategy in the management of diabetes.

HDL promotes adiponectin gene expression via the CAMKK/CAMKIV pathway.

Adiponectin (APN) is an adipokine that protects against diabetes and atherosclerosis. High-density lipoprotein (HDL) mediates reverse cholesterol transport, which also protects against atherosclerosis. In this process, the human homolog of the B class type I scavenger receptor (SR-BI/CLA-1) facilitates the cellular uptake of cholesterol from HDL. The level of circulating APN is positively correlated with the serum level of HDL-cholesterol. In this study, we investigated whether HDL stimulates the gene expression of APN through the Ca2+/calmodulin (CaM)-dependent protein kinase IV (CaMKIV) cascade. APN expression was examined using real-time PCR and western blot analysis in 3T3-L1 cells incubated with HDL. CaMKIV activity was assessed by the detection of activation loop phosphorylation (at Thr196 residue), and the effect of the constitutively active form, CaMKIVc, on APN promoter activity was investigated. Our results showed that HDL stimulated APN gene expression via hSR-BI/CLA-1. Furthermore, we explored the signaling pathways by which HDL stimulated APN expression in 3T3-L1 cells. The stimulation of APN gene expression by HDL appears to be mediated by CaMKK, as STO-609, a specific inhibitor of CaMKK2, prevents this effect. We revealed that CaMKIVc increased APN gene transcriptional activity, and the CaMKIV-dominant negative mutant blocked the effect of HDL on APN promoter activity. Finally, knockdown of hSR-BI/CLA-1 also canceled the effect of HDL on APN gene expression. These results suggest that HDL has an important role to improve the function of adipocytes by activating hSR-BI/CLA-1, and CaMKK/CaMKIV pathway is conceivable as one of the signaling pathways of this activation mechanism.

Effects of Adiponectin on Glucose Metabolism in the Hepatopancreas of Grass Carp (Ctenopharyngodon idella)

Adiponectin plays critical roles in the regulation of energy metabolism in mammals. However, its roles in fish remain to be evaluated. In this study, we examined the tissue distribution characteristics of two adiponectin genes, namely, adipoqa and adipoqb, at transcriptional level, and detected the changes of their mRNA expressions during oral glucose tolerance test (OGTT). Furthermore, we prepared recombinant proteins of grass carp adiponectin A and adiponectin B and studied their roles in the regulation of glucose metabolism in the hepatopancreas of grass carp in vivo. The results showed that adipoqa mRNA was mainly expressed in the heart of grass carp, followed by red muscle, white muscle, and adipose tissue, while adipoqb mRNA was highly expressed in adipose tissue, red muscle, and white muscle. The mRNA levels of adipoqa and adipoqb in the white muscle and heart were significantly decreased at 1 h post OGTT, and their expressions in the heart were also suppressed at 3 h, whereas the transcriptional levels of adipoqa and adipoqb in the red muscle were elevated significantly at 12 h after glucose load. Intraperitoneal injection of adiponectin A or adiponectin B reduced basal serum glucose levels of grass carp and caused an increase of glycogen content in the hepatopancreas. Adiponectin A upregulated the expression of enzyme genes related to glycolysis (gk and pk) and glycogen synthesis (gys) in the hepatopancreas, and adiponectin B promoted the expression of pk and gys, as well as g6pase in the glycogenetic pathway. Besides, adiponectin A and adiponectin B have opposite regulatory effects on glut2 mRNA expression. These results suggested that adiponectin A and adiponectin B promoted glycolysis, gluconeogenesis, and glycogen synthesis, increased glycogen content of hepatopancreas, and reduced basal blood glucose level, and they may have an antagonistic regulatory mechanism in regulating glucose uptake.

Relationship between Epicardial and Coronary Adipose Tissue and the Expression of Adiponectin, Leptin, and Interleukin 6 in Patients with Coronary Artery Disease.

Adipose tissue (AT) is an endocrine and paracrine organ that synthesizes biologically active adipocytokines, which affect inflammation, fibrosis, and atherogenesis. Epicardial and perivascular fat depots are of great interest to researchers, owing to their potential effects on the myocardium and blood vessels. The aim of the study was to assess the expression and secretion of adipocytokine genes in the AT of patients with coronary artery disease (CAD) and patients with aortic or mitral valve replacement. This study included 84 patients with CAD and 50 patients with aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous, epicardial (EAT), and perivascular AT (PVAT), and were cultured for 24 h. EAT exhibited the lowest level of adiponectin gene expression and secretion, regardless of nosology, and high expression levels of the leptin gene and interleukin-6 (IL-6). However, EAT adipocytes in patients with CAD were characterized by more pronounced changes in comparison with the group with heart defects. High leptin and IL-6 levels resulted in increased pro-inflammatory activity, as observed in both EAT and PVAT adipocytes, especially in individuals with CAD. Therefore, our results revealed the pathogenetic significance of alterations in the adipokine and cytokine status of adipocytes of EAT and PVAT in patients with CAD.

Genetic polymorphisms and plasma concentrations of leptin (rs7799039) and adiponectin (rs17300539) are associated with obesity in children and adolescents.

ABSTRACTObjective:The aim of this study was to compare the anthropometric, biochemical, and hormonal characteristics and the presence of genetic polymorphisms of leptin, adiponectin, and tumor necrosis factor alpha (TNF-α) between eutrophic and obese children and adolescents.Methods:This is a case–control study involving 104 children and adolescents. All subjects were assessed for anthropometric characteristics and clinical, laboratory, and genetic polymorphism parameters. The sample was selected from the pediatric endocrinology outpatient clinic specialized in the treatment of obesity in children and adolescents according to the Centers for Disease Control and Prevention (CDC) classification, and controls were selected from the same location in the general pediatric outpatient clinic.Results:As a result, the parameters, such as black color, obese parents, hypertensive parents, and early weaning, were found to be associated with obesity. Increased levels of insulin, triglyceride, total cholesterol, LDL cholesterol, CRP-U, AST, ALT, GGT, free T4, IGF-1, and uric acid and low levels of HDL cholesterol are found to be associated with a higher chance of obesity. The presence of AG/AA polymorphisms in the leptin is associated with a 290% (OR 3.9) higher chance of obesity, and for adiponectin genes, the chances are 740% (OR 8.4) higher. In these obese children and adolescents with AG/AA haplotypes, serum leptin levels were increased and adiponectin levels were decreased in eutrophic individuals, whereas serum TNF-α levels did not change.Conclusions:The AG/AA polymorphisms in the leptin and adiponectin genes alter the serum levels of these adipokines and predispose them to obesity, and many anthropometric, biochemical, and hormonal markers are altered, demonstrating early consequences for the health of these obese children and adolescents.

Role of the variant rs3774261 of adiponectin gene on adiponectin levels and ratio adiponectin/leptin after biliopancreatic diversion in morbid obese subjects.

Single nucleotide variants (SNVs) of ADIPOQ gene on different comorbidities are related to obesity and weight loss. Despite, there are no studies evaluating the effect of rs3774261 on metabolic variables after bariatric surgery. We evaluated the effect of SNV rs3774261 of ADIPOQ gene on biochemical changes after biliopancreatic diversion surgery in morbidly obese subjects for 3 years follow-up. One hundred and forty-nine patients (111 females/38 males) with morbid obesity (body mass index >40 kg/m2) without diabetes mellitus type 2 were enrolled. Biochemical and anthropometric evaluation were registered before and after 1, 2, and 3 years. Genotype of rs3774261 has been studied. Total cholesterol, LDL-cholesterol and triglyceride levels decreased in all genotype groups during the study. Although the improvement in glucose, insulin and HOMA-IR was significant in two genotypes (AA and AG); these changes were earlier in the AA genotype than in Ag and GG genotypes. Adiponectin levels increased in a significant way in subjects with AA genotype in the 3 follow-up periods (first year delta: 16.4±0.5 ng/ml; p=0.03, second year delta: 21.3±0.5 ng/ mL; p=0.02 and third year delta: 23.6±0.7 ng/mL; p=0.01) and at 3 years in subjects with AG genotype (delta: 18.3±0.4 ng/ mL; p=0.03). The ratio adiponectin/leptin increased in a significant way in subjects with AA genotype in the 3 follow-up times (first year delta: 0.40±0.1 units; p=0.02, second year delta: 0.58±0.1 units; p=0.01 and third year delta: 0.65±0.1 ng/mL; p=0.01) and at 3 years in subjects with AG genotype (delta: 0.61±0.1 ng/ mL; p=0.02). Subjects with GG genotype did not show a significant improvement in these parameters during the follow-up. G allele carriers of rs3774261 showed a delay in the improvement of glucose metabolism parameters, adiponectin and adiponectin/leptin ratio.

Adiponectin Gene Polymorphism (rs17300539) Has No Influence on the Occurrence of Metabolic Syndrome in Women with Polycystic Ovary Syndrome.

Adiponectin (rs17300539) is implicated in the pathogenesis of metabolic syndrome (MS), a common comorbidity of polycystic ovarian syndrome (PCOS). The aim of this study was to analyze the association between adiponectin gene polymorphism and incidence of MS in patients with PCOS. The study included 201 women (age 18 to 35 years), among them 81 patients with PCOS without concomitant MS, 70 subjects with PCOS and concomitant, and 50 regularly menstruating controls. Adiponectin gene polymorphism (11391 G/A, rs17300539) was determined by means of a real-time PCR. The study groups did not differ significantly in terms of their age and frequencies of various genotypes of the adiponectin gene polymorphism. The largest proportion in the whole group was Caucasian women (n = 178, 88.56%), who carried the GG genotype of the polymorphism; frequencies of GA and AA genotypes in the whole study group were 10.94% (n = 22) and 0.5% (n = 1), respectively. The presence of G or A allele of the rs17300539 adiponectin gene polymorphism was not associated with a greater likelihood of PCOS with/without concomitant MS. The hereby presented findings imply that MS is a common comorbidity in women with PCOS. However, the incidence of concomitant MS does not seem to be associated with adiponectin gene polymorphism.

Adiponectin gene polymorphisms and risk of type 2 diabetes: an updated evidence for meta-analysis

BackgroundGrowing body of evidence suggest the association between SNP − 11377 C > G and SNP + 276 G > T polymorphisms of adiponectin gene with type 2 diabetes (T2D). However, these findings have not been conclusive and consistent. The present study quantitatively evaluates the data on the association between DIPOQ − 11377C/G, and + 276G/T polymorphisms and risk of T2D through a meta-analysis.MethodsA systematic search was performed in the PubMed, Web of science, Scopus and Cochrane library databases to extract published studies according to the inclusion criteria. Among the 741 studies, 391 of them were screened as full text and 31 studies were finally included in the meta-analysis. Analysis of data was performed using random-effects model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to analyze the strength of association. Subgroup and meta-regression analyses were performed to identify the potential source of heterogeneity.ResultsThe pooled analysis showed that there was no statistically significant association between genotypes of CC (OR = 0.76, 95% CI: 0.53–1.09, P = 0.14), CG (OR = 0.93, 95% CI: 0.72–1.20, P = 0.58) and GG (OR = 1, 95% CI: 0.80–1.26, P = 0.94) ADIPO − 11377 polymorphism with increased risk of T2D. In addition, the results revealed a trend toward an increased risk of T2D for the SNP + 276 TT genotype (OR = 0.87, 95% CI: 0.77–0.98, P = 0.026) as compared with the GT and GG genotypes. Subgroup analysis by ethnicity indicated significant association between the TT genotype of the SNP + 276 and increased risk of T2D among Europeans. Met-regression demonstrated significant association between the GT genotype of + 276 polymorphism with risk of T2D in male individuals (slope: 0.0006; 95% CI: 0.0002–0.0009; P < 0.001).ConclusionsCollectively, our findings demonstrated a positive association between ADIPOQ + 276 G > T polymorphism with increased risk of T2D in male individuals with European ethnicity.Graphical

PPARα/γ, adiponectin, and GLUT4 overexpression induced by moronic acid methyl ester influenced glucose and triglyceride levels of experimental diabetic mice.

The current study aimed to determine the antidiabetic and antidyslipidemic activities of moronic acid methyl ester (1) (compound 1) by in vivo, in vitro, in silico, and molecular biology studies. Compound 1 was evaluated to establish its dose-dependent antidiabetic and antihyperglycemic (50mg/kg) activities, in diabetic and normoglycemic male CD1 mice, respectively. Also, compound 1 was subjected to a subacute study (50mg/kg per day for 8 days) to determine blood biochemical profiles and the expression of protein tyrosine phosphatase 1B (PTP-1B), glucose transporter type 4 (GLUT4), peroxisome proliferator-activated receptor α (PPAR-α), PPAR-γ, adiponectin, interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) in adipose tissue of animals after treatment. Different doses in acute administration of compound 1 decreased glycemia (p< 0.05) compared with vehicle, showing greater effectiveness in the range 50-160mg/kg. Also, the oral glucose tolerance test showed that compound 1 induced a significant antihyperglycemic action by opposing the hyperglycemic peak (p< 0.05). Moreover, compound 1 subacute administration decreased glucose and triglyceride levels after treatment (p< 0.05); while the expression of PPAR-α and PPAR-γ, adiponectin, and GLUT4 displayed an increase (p< 0.05) compared with the diabetic control group. In conclusion, compound 1 showed antihyperglycemic, antidiabetic, and antidyslipidemic effects in normal and diabetic mice, probably due to insulin sensitization through increased mRNA expression of GLUT4, PPAR-α, PPAR-γ, and adiponectin genes.

Genetic Risk Analysis of Gestational Diabetes Mellitus in a Turkish Population

Background: Gestational diabetes mellitus (GDM) is a type of clinical diabetes characterized by insulin resistance and impaired insulin secretion because of environmental and genetic factors. The high risk of developing type 2 diabetes (T2D) in women with GDM and the high risk of developing GDM in women with a family history of T2D suggests that both diseases may have the same genetic basis. Therefore, genes and risk variants associated with the genetic architecture of T2D are being investigated for their effects on the development of GDM. In this study, we aim to investigate ABCC8, TCF7L2, Adiponectin, IRS1, and PPARG genes, which are known as T2D risk genes, to understand the genetic basis of GDM in a Turkish population. Materials and Methods: In our study, 74 pregnant women diagnosed with GDM according to the American Diabetes Association criteria and 49 healthy pregnant women were included. DNA isolations were made from peripheral blood cells collected from pregnant women and regions of targeted genes were scanned by the Polimerase Chain Reaction-Restriction fragment length polymorphism (PCR-RFLP) technique. The homeostatic model assessment for insulin resistance (HOMA-IR), which is an indicator of insulin resistance, was calculated for each individual in the biochemical examinations. The associations of genotypes detected in the target gene regions with the disease and their effects on the biochemical phenotypes were analyzed by establishing the dominant, recessive, and additive models along with calculating odd ratios. The P&lt;0.05 was considered statistically significant in all analyses. Results: A statistically significant association was found between R1273R substitution in the ABCC8 gene and GDM under dominant and additive models. No statistically significant correlation was found between the A1369S and e16/-3t→c variants in the ABCC8 gene and the screened variants in other genes and GDM. When the genotype-phenotype association data was evaluated, no association was detected between all the scanned variants and fasting blood sugar while a weak correlation was found between e16/-3t→c in the ABCC8 gene and fasting insulin (P=0.075) and HOMA-IR (P=0.067). Conclusion: ABCC8 (R1273R and e16/-3t→c) gene variants may be a risk factor for the development of GDM in the Turkish population.

CTRP6 rapidly responds to acute nutritional changes, regulating adipose tissue expansion and inflammation in mice.

In chronic obesity, activated adipose tissue proinflammatory cascades are tightly linked to metabolic dysfunction. Yet, close temporal analyses of the responses to obesogenic environment such as high-fat feeding (HFF) in susceptible mouse strains question the causal relationship between inflammation and metabolic dysfunction, and/or raises the possibility that certain inflammatory cascades play adaptive/homeostatic, rather than pathogenic roles. Here, we hypothesized that CTRP6, a C1QTNF family member, may constitute an early responder to acute nutritional changes in adipose tissue, with potential physiological roles. Both 3-days high-fat feeding (3dHFF) and acute obesity reversal [2-wk switch to low-fat diet after 8-wk HFF (8wHFF)] already induced marked changes in whole body fuel utilization. Although adipose tissue expression of classical proinflammatory cytokines (Tnf-α, Ccl2, and Il1b) exhibited no, or only minor, change, C1qtnf6 uniquely increased, and decreased, in response to 3dHFF and acute obesity reversal, respectively. CTRP6 knockout (KO) mouse embryonic fibroblasts (MEFs) exhibited increased adipogenic gene expression (Pparg, Fabp4, and Adipoq) and markedly reduced inflammatory genes (Tnf-α, Ccl2, and Il6) compared with wild-type MEFs, and recombinant CTRP6 induced the opposite gene expression signature, as assessed by RNA sequencing. Consistently, 3dHFF of CTRP6-KO mice induced a greater whole body and adipose tissue weight gain compared with wild-type littermates. Collectively, we propose CTRP6 as a gene that rapidly responds to acute changes in caloric intake, acting in acute overnutrition to induce a "physiological inflammatory response" that limits adipose tissue expansion.NEW & NOTEWORTHY CTRP6 (C1qTNF6), a member of adiponectin gene family, regulates inflammation and metabolism in established obesity. Here, short-term high-fat feeding in mice is shown to increase adipose tissue expression of CTRP6 before changes in the expression of classical inflammatory genes occur. Conversely, CTRP6 expression in adipose tissue decreases early in the course of obesity reversal. Gain- and loss-of-function models suggest CTRP6 as a positive regulator of inflammatory cascades, and a negative regulator of adipogenesis and adipose tissue expansion.

Genetic associated complications of type 2 diabetes mellitus.

According to the International Diabetes Federation, the number of adults (age of 20-79) being diagnosed with diabetes mellitus (DM) have increased from 285 million in year 2009 to 463 million in year 2019 which comprises of 95% type 2 DM patient (T2DM). Research have claimed that genetic predisposition could be one of the factors causing T2DM complications. In addition, T2DM complications cause an incremental risk to mortality. Therefore, this article aims to discuss some complications of T2DM in and their genetic association. The complications that are discussed in this article are diabetic nephropathy, diabetes induced cardiovascular disease, diabetic neuropathy, diabetic foot ulcer (DFU) and Alzheimer's disease (AD). According to the information obtained, genes associated with diabetic nephropathy (DN) are gene GABRR1 and ELMO1 that cause injury to glomerular. Replication of genes FRMD3, CARS and MYO16/IRS2 shown to have link with DN. The increase of gene THBS2, NGAL, PIP, TRAF6 polymorphism, ICAM-1 encoded for rs5498 polymorphism and C667T increase susceptibility towards DN in T2DM patient. Genes associated with cardiovascular diseases are adiponectin gene (ACRP30) and apolipoprotein E (APOE) polymorphism gene with ξ2 allele. Haptoglobin (Hp) 1-1 genotype and mitochondria superoxide dismutase 2 (SOD2) plays a role in cardiovascular events. As for genes related to diabetic neuropathy, janus kinase (JAK), mutation of SCN9A and TRPA1 gene and destruction of miRNA contribute to pathogenesis of diabetic neuropathy among T2DM patients. Expression of cytokine IL-6, IL-10, miR-146a are found to cause diabetic neuropathy. Besides, A1a16Va1 gene polymorphism, an oxidative stress influence was found as one of the gene factors. Diabetic retinopathy (DR) is believed to have association with monocyte chemoattractant protein-1 (MCP-1) and insulin-like growth factor 1 (IGF1). Over-expression of gene ENPP1, IL-6 pro-inflammatory cytokine, ARHGAP22's protein rs3844492 polymorphism and TLR4 heterozygous genotype are contributing to significant pathophysiological process causing DR, while research found increases level of UCP1 gene protects retina cells from oxidative stress. DFU is manifested by slowing in re-epithelialization of keratinocyte, persistence wound inflammation and healing impairment. Re-epithelialization disturbance was caused by E2F3 gene, reduction of Tacl gene encoded substance P causing persistence inflammation while expression of MMp-9 polymorphism contributes to healing impairment. A decrease in HIF-1a gene expression leads to increased risk of pathogenesis, while downregulation of TLR2 increases severity of wound in DFU patients. SNPs alleles has been shown to have significant association between the genetic dispositions of T<inf>2</inf>DM and AD. The progression of AD can be due to the change in DNA methylation of CLOCK gene, followed with worsening of AD by APOE4 gene due to dyslipidemia condition in T2DM patients. Insulin resistance is also a factor that contributes to pathogenesis of AD.

Association of rs266729 and rs16861194 polymorphisms of the ADIPOQ gene with the risk of obesity in residents of the Moscow region

Rationale: The contribution of the adiponectin gene polymorphisms (ADIPOQ, located at 3q27) in the residents of Nigeria and China to the risk of overweight and its association with the risk of arterial hypertension in the European population have been demonstrated.Aim: To identify associations between rs266729 and rs16861194 polymorphisms of the ADIPOQ gene with overweight and obesity in the Moscow region residents.Materials and methods: Identification of rs266729 and rs16861194 polymorphisms of the ADIPOQ gene was carried out in 222 people (140 women and 82 men, aged 25 to 65 years) living in the Moscow region. Genotyping was performed using allele-specific amplification with real-time detection of the results on the CFX96 Real-Time System amplifier (Bio-Rad, USA) and using TaqMan probes complementary to polymorphic DNA regions. To assess an association between these genetic polymorphisms and overweight/obesity, we performed a case control study, with the cases being subjects with body mass index (BMI) of ≥ 30 kg/m2, and the controls those with BMI of &lt; 30 kg/m2.Results: The mean frequency of the minor allele G rs266729 polymorphism of the ADIPOQ gene in the subjects from the Moscow region was 26.8% and similar in men and women. Comparison of the CC and GG genotypes carriers of the rs266729 polymorphism of the ADIPOQ gene in men showed a statistically significant association of the GG genotype to the BMI value (p = 0.04). There were no statistically significant differences between anthropometric indicators (BMI, body fat mass) in the carriers of different rs16861194 polymorphism genotypes of the ADIPOQ. No association between the studied polymorphisms and blood glucose levels and lipid spectrum could be found.Conclusion: The frequency of the minor allele G of the rs266729 polymorphism of the ADIPOQ gene in the subjects from the Moscow region was similar to their rates in the Russian Federation and European countries. In Moscow residents, the rs266729 polymorphism of the ADIPOQ gene (G allele) contributes to the risk of obesity in homozygous carriers (genotype GG). No association of the rs16861194 polymorphism of the ADIPOQ gene with the BMI was found; therefore, this polymorphism cannot be considered as a genetic marker of the obesity risk.

Adiponutrin and Adiponectin Gene Variants in Indonesian Patients with Non-Alcoholic Fatty Liver Disease: a Preliminary Study

BackgroundVariants of adiponutrin (PNPLA3) and adiponectin (ADIPOQ) genes were considered to be associated with non-alcoholic fatty liver disease (NAFLD). Although the prevalence of NAFLD is increasing, there are limited numbers of studies about the association in Indonesian population.ObjectiveTo confirm whether specific variants of adiponutrin (PNPLA3) and adiponectin (ADIPOQ) genes are associated with NAFLD in Indonesian patients.MethodsData and DNA of 152 participants were obtained from a previous study in Dr. Kariadi Hospital, Semarang, Indonesia. PCR-RFLP analysis was performed for detection of PNPLA3 rs738409 and ADIPOQ rs2241767 variants. The diagnosis and severity of NAFLD were assessed according to NAFLD activity score (NAS) based on histopathology assessment of liverbiopsy.ResultsAllele G of PNPLA3rs738409 was associated with NAFLD in both bivariate (p=0.009, OR 2.52, CI 95% 1.25–5.07) and multivariate (p=0.008, OR 2.62, CI 95% 1.29%–5.32%) analysis, while ADIPOQ rs2241767 had no significant association. In NAFLD participants, both genotypes showed allele G was higher in the group of possible non-alcoholic steatohepatitis (NASH) – NASH (NAS &gt;2) than in the simple steatosis group (NAS &lt;2) i.e. 40.0% vs. 3.75% for the rs2241767 variant and 23.75% vs. 1.25% for the rs738409 variant, without significant association.ConclusionVariant PNPLA3 rs738409 was associated with NAFLD incidence in studied population. Among NAFLD participants, the frequency of both variants were found higher in the possible NASH – NASH group, yet needs to be confirmed with more participants and a multicenter study.Data and DNA of 152 participants were obtained from a previous study in Dr. Kariadi Hospital, Semarang, Indonesia. PCR-RFLP analysis was performed for detection of PNPLA3 rs738409 and ADIPOQ rs2241767 variants. The diagnosis and severity of NAFLD were assessed according to NAFLD activity score (NAS) based on histopathology assessment of liverbiopsy.

An 11-gene signature for the prediction of systemic recurrences in colon adenocarcinoma.

BackgroundPrognosis varies among patients within the same colon adenocarcinoma (COAD) stage, indicating the need for reliable molecular markers to enable individualized treatment. This study aimed to investigate gene signatures that can be used for better prognostic prediction of COAD.MethodsGene-expression profiles of COAD patients were obtained from the Gene Expression Omnibus database (n = 332) and The Cancer Genome Atlas database (n = 431). The relationship between gene signature and relapse-free survival was analysed in the training set (n = 93) and validated in the internal validation set (n = 94) and external validation sets (n = 145 and 431).ResultsOverall, 11 genes (N-myc downstream regulated gene 1 [NDRG1], fms-like tyrosine kinase 1 [FLT1], lipopolysaccharide binding protein [LBP], fatty acid binding protein 4 [FABP4], adiponectin gene [ADIPOQ], angiotensinogen gene [AGT], activin A receptor, type II-like kinase 1 [ACVRL1], CC chemokine ligand 11 [CCL11], cell division cycle 42 [CDC42], T-cell receptor alpha variable 9_2 [TRAV9_2], and proopiomelanocortin [POMC]) were identified by univariable and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Based on the risk-score model, the patients were grouped into the high-risk or low-risk groups using the median risk score as the cut-off. The area under the curve (AUC) values for 1-, 3-, and 5-year recurrence were 0.970, 0.849, and 0.859, respectively. Patients in the high-risk group had significantly poorer relapse-free survival than did those in the low-risk group. The predictive accuracy of the 11-gene signature was proven in the validation sets. Our gene signature showed better predictive performance for 1-, 3-, and 5-year recurrence than did the other four models.ConclusionsThe 11-gene signature showed good performance in predicting recurrence in COAD. The accuracy of the signature for prognostic classification requires further confirmation.

Effect of ciglitazone on adipogenic transdifferentiation of bovine skeletal muscle satellite cells.

Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.

Impact of Sex Difference on Interaction between Adiponectin Gene Single Nucleotide Polymorphisms rs2241766, rs17300539 and rs1501299 w Environment Risk Factors of Type 2 Diabetes among the Ardabil Population in Iran

Impact of Sex Difference on Interaction between Adiponectin Gene Single Nucleotide Polymorphisms rs2241766, rs17300539 and rs1501299 w Environment Risk Factors of Type 2 Diabetes among the Ardabil Population in Iran

Expression of adipocytokine in heart fat depots depending on the degree of coronary artery atherosclerosis in patients with coronary artery disease

Background. In coronary artery disease, a change in the adipocytokine content of local fat depots of the heart is observed. However, it has not yet been established whether the expression levels of the studied parameters are really related to the degree of atherosclerotic lesion of the spacecraft.&#x0D; Aims to identify the features of the expression of adiponectin, leptin and IL-6 by adipocytes of epicardial, perivascular and subcutaneous adipose tissue depending on the degree of atherosclerotic lesion of the coronary channel in coronary heart disease.&#x0D; Materials and methods. The study conducted at the Research Institute for Complex Issues of Cardiovascular Disease in 20172020, included 84 patients with coronary heart disease (CAD), of which 39 with a moderate degree of atherosclerotic lesion of the coronary artery (CA) ( 22 points on the SYNTAX Score scale), 20 with severe (2331 points) and 25 with extremely severe ( 32 points). Biopsies of subcutaneous (SAT), epicardial (EAT) and perivascular adipose tissue (PVAT) were obtained during elective coronary artery bypass grafting (CABG). The expression of adipocytokine genes was determined using polymerase chain reaction (real-time PCR) using TaqMan probes and the concentration of the studied adipocytokines in adipocyte culture medium by enzyme immunoassay. Statistical analysis was performed using Statistica 9.0, a one-dimensional and multi-dimensional logistic regression analysis.&#x0D; Results. In CAD in adipocytes of the cardiac fat depot, a shift in the balance of adipocytokines is observed towards increased expression and secretion of leptin, IL-6 and a decrease in adiponectin with maximum manifestation in severe and extremely severe coronary lesions. Adipocytes of EAT were characterized by the minimal expression of the adiponectin gene against the background of the maximum leptin and IL-6 in comparison with adipocytes SAT and PVAT.&#x0D; Conclusions. Low expression of the adiponectin in EAT and PVAT against the background of increased expression of leptin and IL-6 is associated with an increase in the degree of atherosclerotic lesion of the coronary channel.