C1q TNF Related Protein 3 Levels Research Articles

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.

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.

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.

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.

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.

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.

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.

The Effects of Two Different Intensities of Combined Training on C1q/TNF-Related Protein 3 (CTRP3) and Insulin Resistance in Women with Non-alcoholic Fatty Liver Disease

Background: C1q/TNF-related protein (CTRP3) is a potent anti-inflammatory adipokine with activities, such as reduction of glucose level and inhibition of gluconeogenesis in the liver. However, the effect of exercise training on CTRP3 in patients with non-alcoholic fatty liver disease (NAFLD) remains unknown. Objectives: This study was done to investigate the effects of two different intensities of combined training on CTRP3 and insulin resistance in women with NAFLD and compare these two training patterns. Methods: Thirty-three women with NAFLD were randomly divided into three equal groups. Group 1 performed resistance training (RT), along with aerobic interval training (AIT) (2 - 5 intervals of four minutes, 70 - 75% HRmax), group 2 performed RT along with high-intensity interval training (HIIT) (8 - 13 intervals of one minute, 85 - 95% HRmax), and the control group did not participate in any training. The body composition measurements and blood sampling were carried out before and after 12 weeks of training. Data analysis was performed using repeated-measures ANOVA (α ≤ 0.05). Results: After 12 weeks, the CTRP3 level significantly increased in group 1 compared with the control group (P = 0.01) and group 2 (P &lt; 0.001). The fasting glucose and fasting insulin levels significantly decreased in group 1 compared with the control group (P &lt; 0.001 and P = 0.01, respectively). The insulin resistance index decreased in both group 1 and group 2; however, the difference was not significant compared with the control group (P &gt; 0.05). Conclusions: Combined training (RT + AIT) in the present study increased the level of CTRP3; thus, it is likely that women with NAFLD can benefit from this program as a non-pharmacological adjunct treatment to prevent inflammation and progression of the disease.

C1q/TNF-Related Protein 3 (CTRP-3) Deficiency of Adipocytes Affects White Adipose Tissue Mass but Not Systemic CTRP-3 Concentrations

CTRP-3 (C1q/TNF-related protein-3) is an adipokine with endocrine and immunological function. The impact of adipocyte CTRP-3 production on systemic CTRP-3 concentrations and on adipocyte biology is unknown. A murine model of adipocyte CTRP-3 knockout (KO) was established (via the Cre/loxP system). Serum adipokine levels were quantified by ELISA and adipose tissue (AT) gene expression by real-time PCR. Preadipocytes were isolated from AT and differentiated into adipocytes. Comparative transcriptome analysis was applied in adipocytes and liver tissue. Body weight and AT mass were reduced in CTRP-3 KO mice together with decreased serum leptin. In primary cells from visceral AT of KO mice, expression of adiponectin, progranulin, and resistin was induced, while peroxisome proliferator activated receptor γ (PPARγ) was decreased. M1/M2 macrophage polarization markers were shifted to a more anti-inflammatory phenotype. CTRP-3 expression in AT did not contribute to serum concentrations. AT and liver morphology remained unaffected by CTRP-3 KO. Myelin transcription factor 1-like (Myt1l) was identified as a highly upregulated gene. In conclusion, adipocyte CTRP-3 has a role in adipogenesis and AT weight gain whereas adipocyte differentiation is not impaired by CTRP-3 deficiency. Since no effects on circulating CTRP-3 levels were observed, the impact of adipocyte CTRP-3 KO is limited to adipose tissue. Modified AT gene expression indicates a rather anti-inflammatory phenotype.

Up-regulating lncRNA OIP5-AS1 protects neuron injury against cerebral hypoxia-ischemia induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p

BackgroundInflammation and oxidative stress is closely associated with the development of ischemic brain stroke. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a novel identified long non-coding RNA (lncRNA), has been suggested to play an important role in the development of many types of human cancers. However, the functional involvement of OIP5-AS1 in ischemic stroke is still unknown. MethodsQuantitative real-time polymerase chain reaction and /or western blot were conducted to determine the expression profiles of OIP5-AS1, C1q/TNF-related protein 3 (CTRP3) and miR-186-5p in the serum of stroke patients, as well as in the ischemic penumbra of rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury and microglial cells treated with oxygen glucose deprivation/re-oxygenation (OGD/R). Upon selective regulation of OIP5-AS1 and miR-186-5p, the inflammation and oxidative stress responses in microglia/macrophage as well as neurologic functions in MCAO/R rats were detected. Furthermore, the interactions between OIP5-AS1 and miR-186-5p, miR-186-5p and CTRP3 were investigated by RNA immunoprecipitation (RIP) assay, luciferase report assay and bioinformation anaylsis. ResultsWe observed markedly increased infarct volume, neuronal apoptosis, inflammation and oxidative stress responses in the infarcted lesions of MCAO/R rats, in line with down-regulated levels of OIP5-AS1 and CTRP3 while up-regulated miR-186-5p. Functional studies demonstrated that up-regulation of OIP5-AS1 attenuated infarct volume, neuronal apoptosis, microglia/macrophage inflammation and oxidative stress responses induced by MCAO/R or OGD/R. In terms of mechanism, we revealed that OIP5-AS1-miR-186-5p-CTRP3 axis played a vital role in modulating microglia/macrophage activation and neuronal apoptosis. ConclusionUp-regulating lncRNA OIP5-AS1 protects neuron injury against MCAO/R induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p.

CTRP3 protects hippocampal neurons from oxygen-glucose deprivation-induced injury through the AMPK/Nrf2/ARE pathway.

C1q/TNF-related protein 3 (CTRP3), a member of CTRP family, has been found to have neuroprotective effect. In the current study, we investigated the protective role of CTRP3 in hippocampal neurons exposed to oxygen-glucose deprivation/reperfusion (OGD/R). The mRNA and protein levels of CTRP3 in OGD/R-stimulated hippocampal neurons were measured using qRT-PCR and western blot analysis, respectively. CCK-8 assay was performed to assess cell viability. ROS production was measured using the fluorescence probe 2',7'-dichlorofluorescein diacetate (H2DCFDA). The activities of SOD and GPx were determined using ELISA. Cell apoptosis was assessed. Luciferase reporter assay was carried out to assess the activation of ARE). The levels of p-AMPK and Nrf2 were measured using western blot. Our results showed that the expression of CTRP3 was significantly downregulated in hippocampal neuronal cells exposed to OGD/R. Overexpression of CTRP3 improved cell viability of OGD/R-induced hippocampal neurons. In addition, overexpression of CTRP3 attenuated the OGD/R-caused oxidative stress with decreased ROS production and increased activities of SOD and GPx. Moreover, CTRP3 caused a significant increase in bcl-2 expression and decreases in bax expression and caspase-3 activity. Furthermore, CTRP3 overexpression significantly upregulated the levels of p-AMPK and Nrf2, as well induced the activation of ARE in OGD-R-induced hippocampal neurons. CTRP3 upregulated the mRNA expression levels of HO-1, NQO-1 and GPx-3. Additionally, treatment with the inhibitor of AMPK partially reversed the neuroprotective effect of CTRP3 in OGD/R-exposed neurons. CTRP3 exerted protective effect on OGD/R-induced cerebral injury, which was regulated by AMPK/Nrf2/ARE pathway.

Association of Plasma C1q/TNF-Related Protein 3 (CTRP3) in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia characterized by atrial remodeling. Complement C1q tumor necrosis factor-related protein 3 (CTRP3) is one of the adipokines associated with obesity, diabetes, and coronary heart disease. The association between plasma CTRP3 levels and AF is uncertain. The aim of this study was to investigate whether plasma CTRP3 concentrations were correlated with AF. Our study included 75 AF patients who underwent catheter ablation at our hospital and 47 sinus rhythm patients to determine the difference in plasma CTRP3 concentrations. Blood samples before the ablation were collected, and ELISA was used to measure the concentrations of CTRP3. Plasma CTRP3 concentrations were significantly lower in AF patients compared with control group (366.9 ± 105.2 ng/ml vs. 429.1 ± 100.1 ng/ml, p = 0.002). In subgroup studies, patients with persistent AF had lower plasma CTRP3 concentrations than those with paroxysmal AF (328.3 ± 83.3 ng/ml vs. 380.0 ± 109.2 ng/ml, p = 0.037). The concentrations of plasma CTRP3 in the recurrence group after radiofrequency catheter ablation of AF were lower than those in the nonrecurrence group (337.9 ± 77.3 ng/ml vs. 386.6 ± 108.1 ng/ml, p = 0.045). Multivariate regression analysis revealed the independent correlation between plasma CTRP3 level and AF. Plasma CTRP3 concentrations were correlated with the presence of AF and AF recurrence.

CTRP3 and serum triglycerides in children aged 7-10 years.

The prevalence of obesity-related disorders has been steadily increasing over the past couple of decades. Diseases that were once only detected in adults are now prevalent in children, such as hyperlipidemia. The adipose tissue-derived hormonal factor C1q TNF Related Protein 3 (CTRP3) has been linked to triglyceride regulation especially in animal models. However, the relationship between circulating CTRP3 levels and obesity-related disorders in human subjects is controversial. CTRP3 can circulate in different oligomeric complexes: trimeric (<100 kDa), middle molecular weight (100-300 kDa), and high molecular weight (HMW) oligomeric complexes (>300 kDa). Previous work has identified that it is not the total amount of CTRP3 present in the serum, but the specific circulating oligomeric complexes that appear to be indicative of the relationship between CTRP3 and serum lipids levels. However, this work has not been examined in children. Therefore, the purpose of this study was to compare the levels of different oligomeric complexes of CTRP3 and circulating lipid levels among young children (aged 7-10 years). Morphometric data and serum samples were collected and analyzed from a cross-sectional population of 62 children of self-identified Hispanic origin from a community health center, between 2015 and 2016. Serum analysis included adiponectin, insulin, leptin, ghrelin, glucagon, C-reactive peptide, triglyceride, cholesterol, IL-6, TNF, and CTRP3. Correlation analyses were conducted to explore the relationships between CTRP3 and other biomarkers. Total CTRP3 concentrations were significantly positively correlated with total cholesterol and HDL cholesterol. Whereas, HMW CTRP3 was not significantly associated with any variable measured. Conversely, the middle molecular weight (MMW) CTRP3 was negatively correlated with triglycerides levels, and very low-density lipoprotein (VLDL), insulin, and body mass index (BMI). The negative correlations between MMW CTRP3 and triglycerides and VLDLs were particularly strong (r2 = -0.826 and -0.827, respectively). Overall, these data indicate that the circulating oligomeric state of CTRP3 and not just total CTRP3 level is important for understanding the association between CTRP3 and metabolic diseases. Further, this work indicates that MMW CTRP3 plays an important role in triglyceride and VLDL regulation which requires further study.

Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro.

The adipokine CTRP-3 (C1q/TNF-related protein-3) exerts anti-inflammatory and anti-diabetic effects. Its regulation in obesity and during weight loss is unknown. Serum and adipose tissue (AT) samples were obtained from patients (n = 179) undergoing bariatric surgery (BS). Moreover, patients (n = 131) participating in a low-calorie diet (LCD) program were studied. CTRP 3 levels were quantified by ELISA and mRNA expression was analyzed in AT and in 3T3-L1 adipocytes treated with bile acids and incretins. There was a persistent downregulation of CTRP-3 serum levels during weight loss. CTRP-3 expression was higher in subcutaneous than in visceral AT and serum levels of CTRP-3 were positively related to AT expression levels. A rapid decrease of circulating CTRP-3 was observed immediately upon BS, suggesting weight loss-independent regulatory mechanisms. Adipocytes CTRP-3 expression was inhibited by primary bile acid species and GLP 1. Adipocyte-specific CTRP-3 deficiency increased bile acid receptor expression. Circulating CTRP-3 levels are downregulated during weight loss, with a considerable decline occurring immediately upon BS. Mechanisms dependent and independent of weight loss cause the post-surgical decline of CTRP-3. The data strongly argue for regulatory interrelations of CTRP-3 with bile acids and incretin system.

C1q/TNF-Related Protein-3 (CTRP-3) and Pigment Epithelium-Derived Factor (PEDF) Concentrations in Patients with Gestational Diabetes Mellitus: A Case-Control Study.

Background: Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnant women, defined as any degree of glucose intolerance with onset or first detected during pregnancy. Explanation of its pathogenesis is extremely important due to the possibility of preventing serious maternal and fetal complications. The aim of the study was to evaluate the concentrations of two molecules: C1q/tumor necrosis factor-related protein-3 (CTRP-3) and pigment epithelium-derived factor (PEDF) which may possibly participate in GDM development. To our knowledge, this is the first study in pregnant women with GDM evaluating CTRP-3 level. Methods: Serum CTRP-3 and PEDF concentration and clinical characteristics were detected in 172 pregnant women. These women were divided into two groups: normal glucose tolerance group (NGT, n = 54) and gestational diabetes mellitus group (GDM, n = 118). This second group was further divided into two subgroups depending on the treatment used: GDM 1—diet only (n = 75) and GDM 2—insulin treatment (n = 43). Results: Our study did not reveal any statistically significant difference between the concentration of PEDF in the control and GDM group. In our study there was a significantly higher concentration of CTRP-3 evaluated in the peripheral blood serum in patients with gestational diabetes (GDM) compared to those in the control group (8.84 vs. 4.79 ng/mL). Significantly higher values of CTRP-3 were observed in both the diet-treated subgroup and the group with insulin therapy when compared to control group (8.40 and 10.96, respectively vs. 4.79 ng/mL). Conclusion: PEDF concentration does not change in GDM, whereas an increased level of CTRP-3 may point to the key role of this adipokine in the development of GDM.

91-OR: CTRP3, a Novel Adipokine with Anti-inflammatory and Cardioprotective Properties, in Patients with Cardiovascular Diseases and Type 2 Diabetes Mellitus

Cardiovascular diseases (CVD) are the most common cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). C1q TNF-related protein 3 (CTRP3) is a novel adipokine that reduces inflammation and acts cardioprotectively. The aim of our study was to analyze serum levels and gene expression of CTRP3 in subcutaneous and epicardial adipose tissue in patients with CVD and T2DM undergoing elective cardiac surgery. 38 patients with coronary artery disease (CAD) without T2DM (CAD group), 21 subjects with CAD and T2DM (T2DM group) and 18 patients with a valvular defect without CAD or T2DM (nonCAD group) were included into the study. Peripheral blood, subcutaneous (SAT) and epicardial adipose tissue (EAT) were examined at the start and end of elective cardiac surgery. mRNA expression was determined using qRT-PCR. 21 healthy subjects served as controls for serum CTRP3 (C group). Baseline anthropometric and biochemical parameters were comparable in all groups except of higher fasting blood glucose (6.0±1.2 vs. 5.5±0.2 vs. 6.0±0.9 vs. 8.5±0.4 mmol/l for CAD vs. nonCAD vs. C vs. T2DM, p&amp;lt;0.001) and HbA1C (34.2±1.6 vs. 39.1±0.9 vs. 38.7±6.4 vs. 53.1±1.9 mmol/mol, p&amp;lt;0.001) in T2DM group. Compared to controls, all 3 CVD groups showed lower systemic CTRP3 concentrations (65.6±2.2 vs. 69.3±4.7 vs. 64.8±3.5 vs. 90.8±3.7 ng/ml for CAD vs. nonCAD vs. T2DM vs. C, p&amp;lt;0.001). In EAT, we found reduced mRNA expression of CTRP3 in T2DM compared to nonCAD group (0.61±0.27 vs. 6.61±2.33, p=0.005) and a similar, albeit non-significant trend in CAD group (1.55±0.32, p=0.132). Cardiac surgery resulted in a significant decrease in serum CTRP3 in all patients without affecting mRNA expression in EAT or SAT. To conclude, decreased serum levels of CTRP3 in patients with CVD together with reduced mRNA expression in EAT in T2DM subjects with CAD indicate a possible role of CTRP3 in the pathogenesis of cardiovascular complications of type 2 diabetes mellitus. Disclosure H. Kratochvilova: None. B. Kasperova: None. Z. Lacinova: None. I. Lankova: None. J. Trnovska: None. I. Netuka: None. P. Ivak: None. J. Mahrík: None. D. Hlavácek: None. M. Mraz: None. M. Haluzik: Advisory Panel; Self; Lilly Diabetes, Sanofi. Consultant; Self; Ethicon US, LLC. Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novartis AG, Novo Nordisk A/S. Funding Institute for Clinical and Experimental Medicine (00023001); RVOVFN64165; Ministry of Health of the Czech Republic (NV19-02-00118)