C1q/TNF-related Protein-3 Research Articles

Relation between serum sclerostin and CTRP3 levels and bone mineral density in diabetic postmenopausal women

BackgroundOsteoporosis (OP) is a common finding in diabetic patients especially high-risk populations such as postmenopausal women. Sclerostin is a glycoprotein chiefly secreted by mature osteocytes and is considered a main regulator of bone formation. The C1q/TNF-Related Protein 3 (CTRP3) was found to be significantly associated with OP in postmenopausal women. The effect of type 2 diabetes mellitus (T2DM) on sclerostin and CTRP3 levels in postmenopausal women is rarely investigated. The present study aimed to assess the impact of T2DM on sclerostin and CTRP3 levels and their relation to OP in postmenopausal women.MethodsThe study included 60 postmenopausal women with T2DM and 60 age-matched postmenopausal non-diabetic women. Bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry (DEXA). Serum levels of sclerostin and CTRP3 were assessed using enzyme-linked immunosorbent assay (ELISA) technique.ResultsDiabetic group expressed significantly higher serum levels of sclerostin when compared with non-diabetic group (110.0 ± 29.0 versus 51.5 ± 23.2 ng; p < 0.001). Oppositely, CTRP3 were significantly lower in the diabetic group (3.5 ± 3.5 versus 9.9 ± 3.7 ng/ml, p < 0.001). Multivariate logistic regression analysis identified HbA1c levels [OR (95% CI): 0.49 (0.26–0.93), p = 0.028], sclerotin levels [OR (95% CI): 1.06 (1.0-1.012), p = 0.041] and CTRP3 levels [OR (95%) CI: 1.64 (1.0-2.68), p = 0.047] as significant predictors of OP in diabetic patients.ConclusionsSclerostin and CTRP3 levels are involved in OP in postmenopausal diabetic patients.

FOXO6 transcription inhibition of CTRP3 promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signalling.

C1q/TNF-related protein 3 (CTRP3) has been clarified to display its protective roles in cardiac function. The current study is concentrated on exploring the impacts of CTRP3 on myocardial ischaemia. Oxygen and glucose hypoxia/reoxygenation (OGD/R) model was constructed in human cardiac microvascular endothelial cells (HCMECs). Reverse transcription-quantitative polymerase chain reaction and western blot analysis of CTRP3 expression were conducted. CCK-8 assay was to estimate cell activity and lactate dehydrogenase (LDH) assay kit was to test LDH release. TUNEL assay and western blot were to judge apoptosis. Endothelial barrier function was detected by in vitro vascular permeability assay kit. Zonula occludens-1 (ZO-1) expression was evaluated by immunofluorescence assay. The interaction between CTRP3 promoter and Forkhead Box O6 (FOXO6) was predicted by JASPAR database and verified by chromatin immunoprecipitation and luciferase reporter assays. After OGD/R-induced HCMECs were co-transfected with CTRP3 overexpression and FOXO6 overexpression plasmids, the above functional experiments above were conducted again. Lastly, the expression of sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling-related proteins was examined by western blot. CTRP3 was down-regulated in OGD/R-induced HCMECs. CTRP3 enhanced the viability and barrier integrity while reduced the apoptosis and permeability of OGD/R-insulted HCMECs. This process may be regulated by FOXO6 transcription. Also, FOXO6 inhibition-mediated CTRP3 up-regulation activated the SIRT1/Nrf2 signalling. FOXO6 transcription inhibition of CTRP3 promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signalling.

Decreased circulating CTRP3 levels in acute and chronic cardiovascular patients

C1q/TNF-related protein 3 (CTRP3) represents an adipokine with various metabolic and immune-regulatory functions. While circulating CTRP3 has been proposed as a potential biomarker for cardiovascular disease (CVD), current data on CTRP3 regarding coronary artery disease (CAD) remains partially contradictory. This study aimed to investigate CTRP3 levels in chronic and acute settings such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS). A total of 206 patients were classified into three groups: CCS (n = 64), ACS having a first acute event (ACS-1, n = 75), and ACS having a recurrent acute event (ACS-2, n = 67). The control group consisted of 49 healthy individuals. ELISA measurement in peripheral blood revealed decreased CTRP3 levels in all patient groups (p < 0.001) without significant differences between the groups. This effect was exclusively observed in male patients. Females generally exhibited significantly higher CTRP3 plasma levels than males. ROC curve analysis in male patients revealed a valuable predictive potency of plasma CTRP3 in order to identify CAD patients, with a proposed cut-off value of 51.25 ng/mL. The sensitivity and specificity of prediction by CTRP3 were congruent for the subgroups of CCS, ACS-1, and ACS-2 patients. Regulation of circulating CTRP3 levels in murine models of cardiovascular pathophysiology was found to be partly opposite to the clinical findings, with male mice exhibiting higher circulating CTRP3 levels than females. We conclude that circulating CTRP3 levels are decreased in both male CCS and ACS patients. Therefore, CTRP3 might be useful as a biomarker for CAD but not for distinguishing an acute from a chronic setting.Key messagesCTRP3 levels were found to be decreased in both male CCS and ACS patients compared to healthy controls. Plasma CTRP3 has a valuable predictive potency in order to identify CAD patients among men and is therefore proposed as a biomarker for CAD but not for distinguishing between acute and chronic settings.Regulation of circulating CTRP3 levels in murine models of cardiovascular pathophysiology was found to be partly opposite to the clinical findings in men.

Serum CTRP3 concentrations are positively correlated with disease severity in women with postmenopausal osteoporosis: a population-based cross-sectional study.

Osteoporosis is a leading public health problem that contributes to increasingly high rates of osteoporotic vertebral compression fractures among older adults. This study was developed with the goal of assessing serum C1q/TNF-related protein-3 (CTRP3) levels in postmenopausal osteoporosis (PMOP) patients and exploring the correlations between these levels and PMOP severity. A population-based cross-sectional study of old women with osteoporosis was conducted. All women underwent both clinical and dual-energy X-ray absorptiometry examinations. Serum CTRP3, procollagen type I N propeptide (P1NP), and C-terminal telopeptide of type I collagen (CTX-1) concentrations in these patients were measured via ELISA. Bone tumor markers were additionally assessed. Receiver operating characteristic (ROC) analyses were utilized to assess the diagnostic performance of CTRP3 when identifying PMOP. This study included 54 PMOP patients, 62 patients with osteopenia, and 60 age-matched patients without PMOP. Serum CTRP3 concentrations in PMOP patients were significantly lower than in the other two groups. Bone mineral density (BMD) was positively correlated with serum CTRP3 levels in all study participants, whereas it was negatively correlated with levels of P1NP and CTX-1. ROC analyses also suggested that reductions in serum CTRP3 levels may offer value as a diagnostic indicator of PMOP. Present data highlight a close relationship between CTRP3 and PMOP, with lower serum CTRP3 levels being closely associated with BMD, such that they may represent a protective marker for PMOP.

CTRP3 inhibits myocardial fibrosis through the P2X7R-NLRP3 inflammasome pathway in SHR rats.

Reducing hypertensive myocardial fibrosis is the fundamental approach to preventing hypertensive ventricular remodelling. C1q/TNF-related protein-3 (CTRP3) is closely associated with hypertension. However, the role and mechanism of CTRP3 in hypertensive myocardial fibrosis are unclear. In this study, we aimed to explore the effect of CTRP3 on hypertensive myocardial fibrosis and the potential mechanism. WKY and SHR rats were employed, blood pressure, body weight, heart weight, H/BW were measured, and fibrotic-related proteins, CTRP3 and Collagen I were tested in myocardium at 12 and 20 weeks by immunohistochemical staining and Western blotting, respectively. The results showed that compared with the WKY, SBP, DBP, mean arterial pressure and heart rate (HR) were all significantly increased in SHR at 12 and 20 weeks, while heart weight and H/BW were only increased at 20 weeks. Meanwhile, CTRP3 decreased, while Collagen I increased significantly in the SHR rat myocardium at 20 weeks, which compared to the WKY. Moreover, the expression of α-SMA increased from 12 weeks, Collagen I/III and MMP2/9 increased and TIMP-2 decreased until 20 weeks. In order to explore the function and mechanism of CTRP3 in hypertensive fibrosis, Angiotensin II (Ang II) was used to induce hypertension in primary neonatal rat cardiac fibroblasts in vitro . CTRP3 significantly inhibited the Ang II induced activation of fibrotic proteins, purinergic 2X7 receptor (P2X7R)-NLRP3 inflammasome pathway. The P2X7R agonist BzATP significantly exacerbated Ang II-induced NLRP3 inflammasome activation, which was decreased by the P2X7R antagonists A43079, CTRP3 and MCC950. CTRP3 expression was decreased in the myocardium of SHR rats, and exogenous CTRP3 inhibited Ang II-induced fibrosis in cardiac fibroblasts by regulating the P2X7R-NLRP3 inflammasome pathway, suggesting that CTRP3 is a potential drug for alleviating myocardial fibrosis in hypertensive conditions.

Keloid Core Factor CTRP3 Overexpression Significantly Controlled TGF-β1-Induced Propagation and Migration in Keloid Fibroblasts.

Keloid is a type of benign fibrous proliferative tumor characterized by excessive scarring. C1q/TNF-related protein 3 (CTRP3) has been proven to possess antifibrotic effect. Here, we explored the role of CTRP3 in keloid. In the current research, we examined the influence of CTRP3 on keloid fibroblasts (KFs) and investigated the potential molecular mechanism. KF tissue specimens and adjacent normal fibroblast (NF) tissues were collected cultured from 10 keloid participants. For the TGF-β1 stimulation group, KFs were processed with human recombinant TGF-β1. Cell transfection of pcDNA3.1-CTRP3 or pcDNA3.1 was performed. The siRNA of CTRP3 (si-CTRP3) or negative control siRNA (si-scramble) was transfected into KFs. CTRP3 was downregulated in keloid tissues and KFs. CTRP3 overexpression significantly controlled TGF-β1-induced propagation and migration in KFs. Col I, α-SMA, and fibronectin mRNA and protein levels were enhanced by TGF-β1 stimulation, whereas they were inhibited by CTRP3 overexpression. In contrast, CTRP3 knockdown exhibited the opposite effect. In addition, CTRP3 attenuated TGF-β receptors TRI and TRII in TGF-β1-induced KFs. Furthermore, CTRP3 prevented TGF-β1-stimulated nuclear translocation of smad2 and smad3 and suppressed the expression levels of p-smad2 and p-smad3 in KFs. CTRP3 exerted an antifibrotic role through inhibiting proliferation, migration, and ECM accumulation of KFs via regulating TGF-β1/Smad signal path.

Clinical Diagnostic Values of C1q/TNF-Related Protein-3 for Polycystic Ovary Syndrome Women with Insulin Resistance.

Polycystic ovary syndrome (PCOS) is the most common disease caused by complex endocrine and metabolic abnormalities in women. Insulin resistance is considered an important pathophysiological factor in the pathogenesis of PCOS. Here we investigated the clinical values of C1q/TNF-related protein-3 (CTRP3) as predictive factor for insulin resistance. Our study included 200 patients with PCOS, among which 108 had insulin resistance. Serum CTRP3 levels were measured using enzyme-linked immunosorbent assay. Predictive values of CTRP3 for insulin resistance was analyzed using receiver operating characteristic (ROC) analysis. Correlations of CTRP3 to insulin levels, obesity measurements and blood lipid levels were determined using Spearman's correlation analysis. Our data suggested that PCOS patients with insulin resistance had a higher obesity, lower high-density lipoprotein cholesterol, higher total cholesterol, higher insulin levels and lower CTRP3 levels. CTRP3 had a high sensitivity (72.22%) and specificity (72.83%). CTRP3 significantly correlated to insulin levels, body mass index, waist-to-hip ratio, high-density lipoprotein, and total cholesterol levels. The predictive value of CTRP3 in PCOS patients with insulin resistance was supported by our data. Our findings suggest that CTRP3 is involved in the pathogenesis and insulin resistance of PCOS, which indicates its value as an indicator for the PCOS diagnosis.

Relationship between Parameters of Adipokine and Lipid Profiles in Patients with Acute Myocardial Infarction and Type 2 Diabetes Mellitus

Introduction. Nowadays, it becomes topical to search for methods of diagnosis and treatment for polymorbid patients. The importance of the study on pathophysiological mechanisms of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (DM) has been shown. The aim of the study: to examine the relationship between adipokine and lipid profiles in AMI patients with the presence or absence of type 2 DM. Material and methods. The study was conducted over a period from September 1, 2018 to December 31, 2020. A total of 134 patients with ST-segment elevation AMI in the presence or absence of type 2 DM aged 58.97 ± 7.92 years hospitalized in the intensive care unit of Government Institution “L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” and Kharkiv Railway Clinical Hospital No. 1 of the branch “Center of Healthcare” were enrolled in the study. Group 1 included 74 patients with AMI and type 2 DM aged 59.42 ± 7.66 years. Group 2 (comparison group) comprised 60 patients with AMI without type 2 DM aged 58.42 ± 8.25 years. The control group consisted of 20 otherwise healthy individuals. Serum concentrations of fatty acid-binding protein 4 (FABP4) and C1q/TNF-related protein 3 (CTRP3) of patients were measured by enzyme-linked immunosorbent assay. Serum total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were analyzed by peroxidase enzymatic method. Triglyceride (TG) levels were measured by enzymatic colorimetric method. The atherogenic index was calculated by the A.M. Klimov formula. The levels of very low-density lipoprotein (VLDL) cholesterol and low-density lipoprotein (LDL) cholesterol were estimated by the Friedewald formula. Results and discussion. The patients in Group 1 were found to have higher levels of serum TG in comparison with Group 2 patients (р&lt;0.05). In groups 1 and 2, there was an upward tendency in the levels of TC and LDL (р&gt;0.05), as well as a significant 4.04 and 2.92 times increase in VLDL, respectively, as compared to the control group (p&lt;0.05). The serum levels of FABP4 were significantly increased, while CTRP3 levels were decreased in AMI patients compared to those in otherwise healthy individuals (р&lt;0.05). In AMI patients with type 2 DM (group 1), an inverse correlation was found between FABP4 and VLDL (r = 0.502, p&lt;0.05), TG (r = 0.596, p&lt;0.001); between CTRP3 and TC (r = -0.507, p&lt;0.05), LDL (r = -0.512, p&lt;0.05). In patients with AMI (group 2), an inverse correlation was revealed between FABP4 and VLDL (r = 0.453, p = 0.006), TG (r = 0.439, p = 0.009); between CTRP3 and TC (r = -0.413, p = 0.001), LDL (r = -0.429, p = 0.01). Conclusions. The characteristics of changes in the FABP4 and CTRP3 serum levels are evidence of an adipokine metabolism imbalance in AMI with the presence or absence of type 2 DM, indicating a metabolic shift in this patient category. The relationship between lipid profile markers and FABP4 and CTRP3 may indicate the influence of the latter on lipid metabolism.

Obesity, chronic kidney disease progression and the role of the adipokine C1q/TNF related protein-3

Introduction and aimsObesity is a risk factor for incident chronic kidney disease (CKD). C1q/TNF related protein 3 (CTRP3) is an adipokine with multiple effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP3 levels and CKD progression. MethodsPatients with stage 3 and 4 CKD without previous cardiovascular events were enrolled and divided into groups according to body mass index (BMI) and sex. Demographic, clinical, analytical data and CTRP3 levels were collected at baseline. During follow-up, renal events (defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate were registered). Results81 patients were enrolled. 27 were obese and 54 non-obese. Baseline CTRP3 was similar between both groups (90.1±23.8 vs 84.5±6.2; p=0.28). Of the sum, 54 were men and 27 women, with higher CTRP3 in women (81.4±24.7 vs 106±24.7;p<0.01). During a mean follow-up of 68 months, 15 patients had a renal event. Patients in the higher CTRP3 tertile had less events but without statistical significance (p=0.07). Obese patients in the higher CTRP3 tertile significantly had less renal events (p=0.049). By multiple regression analysis CTRP3 levels could not predict renal events (HR 0.98; CI95% 0.96–1.06). ConclusionsCTRP3 levels are higher in woman than men in patients with CKD, with similar levels between obese and non obese. Higher CTRP3 levels at baseline were associated with better renal outcomes in obese patients.

RELATIONSHIP BETWEEN PARAMETERS OF ADIPOKINE AND LIPID PROFILES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION AND TYPE 2 DIABETES MELLITUS

Abstract. Introduction. Nowadays, it becomes topical to search for methods of diagnosis and treatment for polymorbid patients. The importance of the study on pathophysiological mechanisms of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (DM) has been shown. The aim of the study: to examine the relationship between adipokine and lipid profiles in AMI patients with the presence or absence of type 2 DM. Material and methods. The study was conducted over a period from September 1, 2018 to December 31, 2020. A total of 134 patients with ST-segment elevation AMI in the presence or absence of type 2 DM aged 58.97 ± 7.92 years hospitalized in the intensive care unit of Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” and Kharkiv Railway Clinical Hospital No. 1 of the branch “Center of Healthcare” were enrolled in the study. Group 1 included 74 patients with AMI and type 2 DM aged 59.42 ± 7.66 years. Group 2 (comparison group) comprised 60 patients with AMI without type 2 DM aged 58.42 ± 8.25 years. The control group consisted of 20 otherwise healthy individuals. Serum concentrations of fatty acid-binding protein 4 (FABP4) and C1q/TNF-related protein 3 (CTRP3) of patients were measured by enzyme-linked immunosorbent assay. Serum total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were analyzed by peroxidase enzymatic method. Triglyceride (TG) levels were measured by enzymatic colorimetric method. The atherogenic index was calculated by the A.M. Klimov formula. The levels of very low-density lipoprotein (VLDL) cholesterol and low-density lipoprotein (LDL) cholesterol were estimated by the Friedewald formula. Results and discussion. The patients in Group 1 were found to have higher levels of serum TG in comparison with Group 2 patients (р&lt;0.05). In groups 1 and 2, there was an upward tendency in the levels of TC and LDL (р ˃0.05), as well as a significant 4.04 and 2.92 times increase in VLDL, respectively, as compared to the control group (p&lt;0.05). The serum levels of FABP4 were significantly increased, while CTRP3 levels were decreased in AMI patients compared to those in otherwise healthy individuals (р&lt;0.05). In AMI patients with type 2 DM (group 1), an inverse correlation was found between FABP4 and VLDL (r = 0.502, p&lt;0.05), TG (r = 0.596, p&lt;0.001); between CTRP3 and TC (r = -0.507, p&lt;0.05), LDL (r = -0.512, p&lt;0.05). In patients with AMI (group 2), an inverse correlation was revealed between FABP4 and VLDL (r = 0.453, p = 0.006), TG (r = 0.439, p = 0.009); between CTRP3 and TC (r = -0.413, p = 0.001), LDL (r = -0.429, p = 0.01). Conclusions. The characteristics of changes in the FABP4 and CTRP3 serum levels are evidence of an adipokine metabolism imbalance in AMI with the presence or absence of type 2 DM, indicating a metabolic shift in this patient category. The relationship between lipid profile markers and FABP4 and CTRP3 may indicate the influence of the latter on lipid metabolism.

Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia.

Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking. In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI. Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients. Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11.

Circulating Levels of C1q/TNF-Related Protein 3 (CTRP3) and CTRP9 in Gestational Diabetes and Their Association with Insulin Resistance and Inflammatory Cytokines.

Gestational diabetes mellitus (GDM) is closely related to obesity, adipose tissue, and adipokines. Adiponectin-homologous adipokines with anti-inflammatory properties, including C1q/TNF-related protein 3 (CTRP3) and CTRP9, regulate glucose and lipid metabolism, which was measured in pregnant women with GDM with the aim to assess their circulating levels and their relation with inflammatory cytokines and other biochemical data. Serum levels of CTRP3, CTRP9, adiponectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured in 43 subjects with GDM and 42 healthy controls by enzyme-linked immunosorbent assay. Serum levels of adiponectin and CTRP3 were lower in GDM subjects than in controls, whereas CTRP9, TNF-α, and IL-6 showed higher concentrations in subjects with GDM than in controls. In the subjects with GDM, there was a significant association of CTRP3 with homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, and triglycerides, whereas CTRP9 is associated with TNF-α and HOMA-IR. The differences in the assessed levels of CTRP3 and CTRP9 suggest a possible relation with the pathogenesis of GDM, in particular insulin resistance, which showed significant association with both adipokines.

Exenatide increases CTRP3 gene expression in adipose cells by inhibiting adipogenesis and induces apoptosis

Considering the rapidly increasing prevalence of obesity worldwide, the number of weight control drugs is very few. Incretin-based therapies are currently being developed to achieve weight control, and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) are used in incretin-based therapies. This study aimed to investigate the cytotoxicity of exenatide, a GLP-1A, on 3T3-L1 adipocytes and the effect of exenatide on the expression of adipogenesis-related genes, insulin and glucose levels, and apoptosis. Cytotoxic activity of exenatide on 3T3-L1 adipocytes was determined by MTT method. Gene expression levels were determined by qPCR. Apoptosis studies were performed on the Muse Cell Analyzer. C1q/TNF-related protein-3 (CTRP3) expression levels were found to be higher in exenatide treated adipocyte cells than in control cells (p < 0.001). Adipocyte cells treated with exenatide were found to have lower PPAR-γ gene expression levels when compared to control adipocyte cells (p < 0.001). Intracellular insulin (p < 0.001) and glucose levels were higher in 3T3-L1 adipocytes treated with exenatide compared to control adipocyte cells. Total apoptosis increased approximately 1.5 times as a result of exenatide administration. The increase in CTRP3 gene expression, which is thought to be a new biomarker for obesity, and the decrease in PPAR-γ gene expression indicate that exenatide is a promising new pharmacotherapeutic agent in the treatment of obesity by regulating the expression of genes related to adipogenesis and lipogenesis and inducing apoptosis.

Decreased Epicardial CTRP3 mRNA Levels in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease Undergoing Elective Cardiac Surgery: A Possible Association with Coronary Atherosclerosis.

(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM.

Predictive Model for Acute Heart Failure in Patients with Acute Myocardial Infarction and Type 2 Diabetes Mellitus Based on Energy and Adipokine Metabolism Indicators

BACKGROUND: Acute heart failure (AHF) is one of the early complications of acute myocardial infarction (AMI) in diabetic patients. Evaluation of biomarkers of energy and adipokine metabolism can help in the early identification of diabetic patients at risk of AHF. AIM: The present study is aimed to predict the development of AHF in diabetic patients with AMI based on energy and adipokine metabolism parameters. METHODS: A total of 74 diabetic patients with AMI were examined between September 1, 2018, and December 31, 2020. Serum adropin, irisin, and C1q/TNF-related protein 3 (CTRP3) levels were measured by enzyme-linked immunosorbent assay. To predict AHF development in AMI patients, generalized linear mixed model (GLMM) was applied. RESULTS: The serum concentrations of adropin, irisin, and CTRP3 have been found to be reduced in diabetic patients with AMI and AHF. The accuracy of predicting AHF Killip Class 1 was 96.7%, and the accuracy of prediction for AHF Killip Class 2 was 57.1%, that is, the model was poorly sensitive to this level of complications. The prediction accuracy for AHF Killip Class 3 was 80%, that is, the model was highly sensitive to complications of this level, and for AHF Killip Class 4 – 100% being the maximum level of the model sensitivity. CONCLUSIONS: Low serum concentrations of adropin, irisin, and CTRP3 indicate an imbalance in energy and adipokine homeostasis. The constructed model predicts the probability of AHF development with high accuracy of 91.9% in diabetic patients with AMI.

Effects of Different Ovulation Induction Regimens on Sex Hormone Levels and Serum CTRP3 and CTRP15 Levels in Patients with Polycystic Ovary Syndrome (PCOS).

Objective A retrospective cohort study aimed to explore the effects of different ovulation induction regimens on the levels of sex hormones and serum C1q/TNF-related protein-3 (CTRP3) and C1q/TNF-related protein-15 (CTRP15) in patients with PCOS. Methods A total of 100 patients with PCOS treated in the department of gynecology and obstetrics from February 2019 to April 2021 in our hospital were enrolled. The patients were arbitrarily assigned into control group and study group. The treatment effect, pregnancy rate, ovulation rate, follicle size, thickness of endometrium, number of mature follicles and ovulation, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), serum CTRP3, CTRP15 and menstrual score were compared. Results There exhibited no statistical difference in baseline clinical data between the two kinds of patients. The therapeutic effects were compared, the effective rate was 98.00% in the study group, 13 cases in the control group, 20 cases in the effective group and 7 cases in the control group, and the effective rate was 86.00%. The effective rate in the study group was higher (P <0.05). The size of follicles and the thickness of endometrium in the two groups were compared before and after intervention. There exhibited no significant difference in the size of follicles and the thickness of endometrium before and after intervention (P >0.05). The size of follicles and the thickness of endometrium in the study group were significantly higher (P <0.05). The size of follicles and the thickness of endometrium in the study group were significantly higher (P <0.05). There exhibited no significant difference in the number of mature follicles and ovulation before and after intervention (P >0.05). After intervention, the number of mature follicles and ovulation in the two groups increased. The number of mature follicles and ovulation in the study group were (4.76 ± 0.90) and (4.48 ± 0.73), respectively, which were higher compared to the control group (2.45 ± 0.86) and (2.82 ± 0.84), respectively (P <0.05). The levels of serum LH, FSH, E2 and T were not significantly different before and after intervention. After the intervention of different ways of ovulation induction, the levels of serum LH, FSH, E2 and T in the two groups continued to decrease, and the levels of the above sex hormones in the study group were significantly lower (P <0.05). The menstrual score and the levels of serum CTRP3 and CTRP15 were compared before and after intervention. After intervention, the menstrual score of patients in both groups decreased, and the menstrual score of the study group was lower. In addition, the levels of serum CTRP3 and CTRP15 in the two groups decreased after intervention. Compared with the control group, the levels of CTRP3 and CTRP15 in the study group were lower after intervention (P <0.05). The ovulation rate and pregnancy rate of the two groups were compared. In the study group, there were 45 ovulation cases, the ovulation rate was 90.00% (45/50), the pregnancy rate was 33 cases, the pregnancy rate was 66.00% (33/50), and the ovulation rate in the control group was 31 cases, the ovulation rate was 62.00% (31/50), the pregnancy rate was 20 cases, and the pregnancy rate was 40.00% (20/50). The ovulation rate and pregnancy rate in the study group were higher (P <0.05). Conclusion Different ovulation induction regimens have different effects on the levels of sex hormones and serum CTRP3 and CTRP15 in patients with PCOS. Long-acting follicular phase regimens can effectively promote the therapeutic effect of patients and increase the ovulation rate and pregnancy rate. In addition, it can also reduce the levels of serum LH, follicle stimulating FSH, E2 and testosterone T, and help to promote the levels of serum CTRP3 and CTRP15, which is worth popularizing and applying in clinic.

Obesity, chronic kidney disease progression and the role of the adipokine C1q/TNF related protein-3

Introduction and aimsObesity is a risk factor for incident chronic kidney disease (CKD). C1q/TNF related protein 3 (CTRP3) is an adipokine with multiple effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP3 levels and CKD progression. MethodsPatients with stage 3 and 4 CKD without previous cardiovascular events were enrolled and divided into groups according to body mass index (BMI) and sex. Demographic, clinical, analytical data and CTRP3 levels were collected at baseline. During follow-up, renal events (defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate were registered). Results81 patients were enrolled. 27 were obese and 54 non-obese. Baseline CTRP3 was similar between both groups (90.1±23.8 vs 84.5±6.2; p=0.28). Of the sum, 54 were men and 27 women, with higher CTRP3 in women (81.4±24.7 vs 106±24.7;p<0.01). During a mean follow-up of 68 months, 15 patients had a renal event. Patients in the higher CTRP3 tertile had less events but without statistical significance (p=0.07). Obese patients in the higher CTRP3 tertile significantly had less renal events (p=0.049). By multiple regression analysis CTRP3 levels could not predict renal events (HR 0.98; CI95% 0.96–1.06). ConclusionsCTRP3 levels are higher in woman than men in patients with CKD, with similar levels between obese and non obese. Higher CTRP3 levels at baseline were associated with better renal outcomes in obese patients.

Determination of the temporary disability duration in patientswith acute myocardial infarction depending on the body mass index

Prolonged temporary disability in patients with acute myocardial infarction (AMI) is more common in the presence of concomitant abnormalities. Adipokine C1q/TNF-related protein 3 (CTRP-3) is produced by adipose tissue and exhibits anti-inflammatory and cardioprotective properties. The course and prognosis of AMI depend on the presence of comorbid disorders and hence are objects of scientific interest. Aim. To identify risk factors affecting the temporary disability duration in AMI patients depending on body mass index (BMI). Materials and methods. The study involved 189 patients with ST-segment elevation AMI who were divided into 3 groups depending on BMI. The first group included 60 patients with AMI and normal BMI, the second group comprised 68 patients with AMI and excess body weight (EBW) and the third group was composed of 61 AMI patients with obesity. CTRP-3 was determined by enzyme-linked immunosorbent assay. Statistical data were processed using the licensed software package IBM SPPS Statistics (version 27.0). Significance of differences between normally distributed mean values of quantitative variables was assessed by ANOVA with Bonferroni correction for multiple comparisons. The logistic regression method was used to determine the period of temporary disability. The difference was considered significant at a P value ˂ 0.05. Results. In analyzing the studied indicators, a significant decrease in the concentration of CTRP-3 was found in AMI patients with obesity on the first day compared to AMI patients with normal BMI (P &lt; 0.001), which indicated the effect of obesity on the AMI development. The following indicators were determined to construct a model for predicting the duration of temporary disability, namely CTRP-3 on day 1, glucose on day 1, the presence of permanent atrial fibrillation, early complicationsof AMI. Conclusions. The proposed method helped to determine the duration of temporary disability in patients with AMI depending on BMI, which would improve the provision of high-quality diagnostics and treatment of patients by reducing the economic costs of the length of hospital stay.

Transgenic overexpression of CTRP3 does not prevent alcohol induced hepatic steatosis in female mice.

Alcoholic liver disease (ALD) is one of the leading causes of morbidity and mortality from hepatic complications. C1q/TNF-related protein 3 (CTRP3) is an adiponectin paralog and, in male mice, increased levels of circulating CTRP3 prevents ALD. Therefore, the purpose of this study was to replicate the observed hepatoprotective effect of elevated circulating CTRP3 levels in female mice. Twelve-week-old female wildtype and CTRP3 overexpressing transgenic mice were fed the Lieber-DeCarli alcohol-containing liquid diet (5% vol/vol) for 6 weeks. Unlike the previous study with male mice, CTRP3 overexpression provided no attenuation to alcohol-induced hepatic lipid accumulation, cytokine production, or overall mortality. In conclusion, there appears to be a clear sex-specific effect of CTRP3 in response to alcohol consumption that needs to be explored further.

Взаємозв’язок між показниками адипокінового та ліпідного профілю у пацієнтів на гострий інфаркт міокарда та цукровий діабет 2 типу

Introduction. Nowadays, it becomes topical to search for methods of diagnosis and treatment for polymorbid patients. The importance of the study on pathophysiological mechanisms of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (DM) has been shown. The aim of the study: to examine the relationship between adipokine and lipid profiles in AMI patients with the presence or absence of type 2 DM. Material and methods. The study was conducted over a period from September 1, 2018 to December 31, 2020. A total of 134 patients with ST-segment elevation AMI in the presence or absence of type 2 DM aged 58.97 ± 7.92 years hospitalized in the intensive care unit of Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” and Kharkiv Railway Clinical Hospital No. 1 of the branch “Center of Healthcare” were enrolled in the study. Group 1 included 74 patients with AMI and type 2 DM aged 59.42 ± 7.66 years. Group 2 (comparison group) comprised 60 patients with AMI without type 2 DM aged 58.42 ± 8.25 years. The control group consisted of 20 otherwise healthy individuals. Serum concentrations of fatty acid-binding protein 4 (FABP4) and C1q/ TNF-related protein 3 (CTRP3) of patients were measured by enzyme-linked immunosorbent assay. Serum total cholesterol (TC) and highdensity lipoprotein (HDL) cholesterol were analyzed by peroxidase enzymatic method. Triglyceride (TG) levels were measured by enzymatic colorimetric method. The atherogenic index was calculated by the A.M. Klimov formula. The levels of very low-density lipoprotein (VLDL) cholesterol and low-density lipoprotein (LDL) cholesterol were estimated by the Friedewald formula. Results and discussion. The patients in Group 1 were found to have higher levels of serum TG in comparison with Group 2 patients (р&lt;0.05). In groups 1 and 2, there was an upward tendency in the levels of TC and LDL (р ˃0.05), as well as a significant 4.04 and 2.92 times increase in VLDL, respectively, as compared to the control group (p&lt;0.05). The serum levels of FABP4 were significantly increased, while CTRP3 levels were decreased in AMI patients compared to those in otherwise healthy individuals (р&lt;0.05). In AMI patients with type 2 DM (group 1), an inverse correlation was found between FABP4 and VLDL (r = 0.502, p&lt;0.05), TG (r = 0.596, p&lt;0.001); between CTRP3 and TC (r = -0.507, p&lt;0.05), LDL (r = -0.512, p&lt;0.05). In patients with AMI (group 2), an inverse correlation was revealed between FABP4 and VLDL (r = 0.453, p = 0.006), TG (r = 0.439, p = 0.009); between CTRP3 and TC (r = -0.413, p = 0.001), LDL (r = -0.429, p = 0.01). Conclusions. The characteristics of changes in the FABP4 and CTRP3 serum levels are evidence of an adipokine metabolism imbalance in AMI with the presence or absence of type 2 DM, indicating a metabolic shift in this patient category. The relationship between lipid profile markers and FABP4 and CTRP3 may indicate the influence of the latter on lipid metabolism.