Serum C1q/TNF-related Protein 9 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.

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.

The Impact of Obesity on C1q/TNF-Related Protein-9 Expression and Endothelial Function following Acute High-Intensity Interval Exercise vs. Continuous Moderate-Intensity Exercise.

C1q-TNF-related protein-9 (CTRP9) increases endothelial nitric oxide synthase and reduces vasoconstrictors. There is limited information regarding exercise-mediated CTRP9 in obesity. The purpose of this study was to compare high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CME) on the CTRP9 response and an indicator of endothelial function (FMD) in obese participants. Sixteen young male participants (9 obese and 7 normal-weight) participated in a counterbalanced and caloric equated experiment: HIIE (30 min, 4 intervals of 4 min at 80-90% of VO2 max with 3 min rest between intervals) and CME (38 min at 50-60% VO2 max). Serum CTRP9 and FMD were measured prior to, immediately following exercise, and 1 h and 2 h into recovery. CTRP9 was significantly increased immediately following acute HIIE and CME in both groups (p = 0.003). There was a greater CME-induced FMD response at 2 h into recovery in obese participants (p = 0.009). A positive correlation between CTRP9 and FMD percent change was observed in response to acute CME when combined with both obese and normal-weight participants (r = 0.589, p = 0.016). The novel results from this study provide a foundation for additional examination of the mechanisms of exercise-mediated CTRP9 on endothelial function in individuals with obesity.

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.

1046-P: Role of Serum C1q/TNF-Related Protein 9 in Predicting Gestational Diabetes Mellitus

Background/Aims: C1q/TNF-related protein 9 (CTRP9) as a member of CTRP super family, participates in the regulation of glycolipid metabolism. However information regarding the role of CTRP9 in gestational diabetes mellitus (GDM) is scarce. The current study aims to ascertain the relationship between serum CTRP9 levels and GDM. Methods: A total of 35 GDM patients and 37 normal pregnant women were enrolled in our study. Serum CTRP9 levels were measured via enzyme-linked immunosorbent assay (ELISA) . Fasting insulin (FINS) , IL-6, Leptin, MCP-1, TNF-α and IL-1β were quantified using Luminex-xMAP technology. Anthropometric data and biochemical parameters were also obtained or measured. Results: The results showed that fasting plasma glucose (FPG) , one hour plasma glucose (1-h PG) , 2 hour plasma glucose (2-h PG) , FINS, IL-6, Leptin, TNF-α and CTRP9 during GDM group were significantly higher than the control group. In addition, serum CTRP9 levels had a significantly positive correlation with FPG (r = 0.559, P &amp;lt; 0.001) , 1h-PG (r = 0.539, P &amp;lt;0.0) , 2h-PG (r = 0.378, P = 0.001) , FINS (r = 0.253, P = 0.032) , HOMA-IR (r = 0.382, P = 0.001) , IL-6 (r = 0.283, P = 0.016) , and TNF-α (r = 0.266, P = 0.024) . Furthermore, binary logistic regression demonstrated that HOMA-IR and CTRP9 were independent risk factors for GDM. The AUC-ROC indicated that the diagnostic efficiency of combined CTRP9 and HOMA-IR was much higher than a single index. Conclusions: The high level of serum CTRP9 is an independent risk factor for GDM. Moreover, the combination of serum CTRP9 and HOMA-IR were more efficient in diagnosing GDM. Key words: Gestational diabetes mellitus, CTRP9, insulin resistance Disclosure H. Zhang: None.

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.

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)

Role of First-Trimester Serum C1q/TNF-Related Protein 9 in Gestational Diabetes Mellitus.

The current study aims to explore the relationship between gestational diabetes mellitus (GDM) and C1q/TNF-related protein 9 (CTRP9) level in early pregnancy. Clinical data of 63 GDM patients and 70 normal pregnant women were included in the present study. Binary logistic regression analysis was used to explore the risk factors for GDM. To determine the value of CTPR9 for predicting GDM, the area under the receiver operating characteristic curve (AUC-ROC) was analyzed. Pearson's correlation assay was performed to explore the relationship between serum CTRP9 and body mass index (BMI) or oral glucose tolerance test (OGTT). Our data showed that the age, median maternal prepregnancy BMI, and fasting blood glucose during pregnancy of GDM group were significantly higher than those of the control group. ELISA showed the level of first-trimester serum CTRP9 was significantly decreased in GDM patients compared with that of healthy controls. Multiple logistic regression analysis showed that first-trimester serum CTRP9 and BMI were risk factors of GDM. The AUC-ROC showed that the diagnostic efficiency of CTRP9 + BMI was much higher than that of BMI alone. Moreover, first-trimester serum CTRP9 was found to be negatively correlated with BMI or OGTT in GDM patients. Serum CTRP9 was an independent risk factor for the progression of GDM in pregnant women. Combined use of first-trimester serum CTRP9 and maternal pre-pregnancy BMI may be able to more accurately predict the occurrence of GDM.

Association of circulating CTRP9 with soluble adhesion molecules and inflammatory markers in patients with type 2 diabetes mellitus and coronary artery disease.

C1q/TNF-related protein 9 (CTRP9) is a paralogue of adiponectin with known favorable effects on lipid and glucose metabolism. A potential role of CTRP9 for regulation of endothelium function has been suggested by previous studies. However, no studies have examined the relation between serum CTRP9 levels and adhesion molecules in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). The present study was conducted on 337 subjects who underwent coronary angiography and were categorized into four groups according to the presence of CAD and T2DM (control, CAD, T2DM and CAD+T2DM). Serum levels of CTRP9, adiponectin, sICAM-1, sVCAM-1, sE-Selectin, IL-6 and TNF-α were measured. It was found that the circulating CTRP9 levels were independently associated with increased risk of CAD and T2DM in addition to elevated levels of serum CTRP9 in CAD, T2DM and CAD+T2DM groups. A significant association of serum CTRP9 levels with adhesion molecules in CAD and T2DM patients as well as serum TNF-α levels in CAD individuals was noted. A significant relation between the circulating levels of CTRP9 and HOMA-IR in T2DM subjects was also observed. The results revealed increased circulating levels of CTRP9 in T2DM and CAD individuals which suggests a compensatory response to insulin resistance, inflammatory milieu and endothelial dysfunction; however, more studies are needed to confirm this.

Expression of C1q/TNF-related protein-3 (CTRP3) in serum of patients with gestational diabetes mellitus and its relationship with insulin resistance.

In this study, the changes of insulin resistance (IR) and pancreatic β-cell function in GDM patients were observed, changes of CTRP3 level in fasting serum and relationships with plasma glucose (PG) and pancreatic β-cell function were explored at the same time, and the correlation between serum CTRP3 and body mass index (BMI) was preliminarily discussed, providing a new way to identify the pathogenesis of GDM. Data of women from 24 to 28 weeks of pregnancy were collected. 100 women were selected to form gestational diabetes mellitus (GDM) group and another 100 women were chosen to constitute normal glucose tolerance (NGT) group according to the results of oral glucose tolerance test (OGTT). They were divided into GDM overweight/obesity (GDM + OW) group, GDM non-overweight/obesity (GDM + NW) group, simple overweight (OW) group and normal body weight (NW) group, according to whether the progestational body mass index (BMI) was higher than 24 kg/m2 before pregnancy. General information of all subjects, for example, age, last menstrual period, parity, diet, weight and height, were collected, and blood samples were taken from all subjects for use in detections of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and serum C1q/tumor necrosis factor-related protein-3 (CTRP3). The levels of FPG, 1 h PG, 2 h PG, fasting CP (FCP), fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR), TG and VLDL-C in the GDM group, were significantly higher than those in the NGT group. TC and LDL-C in the GDM group were greater than those in the NGT group. Compared with that in the NGT group, homeostasis model assessment of β (HOMA-β) index was lower in the GDM group. From the NGT group to the GDM group, FPG, 1 h PG, 2 h PG, FINS and FCP had rising tendencies, and the differences were of statistical significance. Pearson correlation analysis indicated that HOMA-IR was positively correlated with pre-pregnancy BMI, FPG, 2 h PG, FINS, 1 h INS, 2 h INS, FCP, 1 h CP and 2 h CP in the GDM group, HOMA-β was negatively related to FPG. In the NGT group, there was a positive correlation between HOMA-IR and pre-pregnancy BMI. The level of CTRP3 in fasting serum of the GDM group was distinctly lower than that of the NGT group. Pearson correlation analysis revealed that in the GDM group, fasting serum CTRP3 had positive correlations with HOMA-β and HDL-C, but negatively associated with pre-pregnancy BMI, FPG, 1 h PG, 2 h PG, FCP, HOMA-IR, TG and VLDL-C. In the NGT group, the fasting serum CTRP3 was negatively correlated with pre-pregnancy BMI. Multiple linear stepwise regression analysis showed FPG was an independent influencing factor for fasting serum CTRP3. With the increase of FPG, the progression of GDM IR patients is increased, and pancreatic β-cell function progressively declines. The decrease of CTRP3 level in fasting serum in GDM patients plays a metabolic role in the pathogenesis of GDM.

Low serum CTRP3 levels are associated with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Nonalcoholic fatty liver disease (NAFLD) commonly occurs in patients with type 2 diabetes mellitus (T2DM). C1q/TNF-related protein-3 (CTRP3) levels are decreased in type 2 diabetic patients. However, to date, it is unknown whether low CTRP3 level are correlated with the incidence of NAFLD. The aim of this study was to observe this association in Chinese patients with T2DM. Overall, 175 newly diagnosed T2DM were recruited in this study. The subjects were divided into NAFLD group (n=93) and control group (n=82). Anthropometric parameters, blood pressure, and several biochemical parameters were measured. The body composition was assessed with the bioelectrical impedance analysis (BIA) method. Insulin level was evaluated by radioimmunoassay. Levels of serum CTRP3 and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Our findings demonstrated that type 2 diabetic patients with NAFLD had lower levels of serum CTRP3 than did those without NAFLD (P=.002). Serum CTRP3 level was negatively correlated with body mass index (r=−0.271, P=.001), visceral fat area (r=−0.285, P<.001), glycosylated hemoglobin A1c (r=−0.270, P<.001), triglycerides (r=−0.267, P<.001), CRP (r=−0.222, P=.010), IL-6 (r=−0.212, P=.008), and HOMA-IR indices (r=−0.334, P<.001). When compared with the highest CTRP3 tertile, the odds ratio of the middle tertile for NAFLD incidence was 4.54 (95% CI, 1.53–13.47) and 5.80 (95% CI, 1.60–21.02) for the lowest tertile after adjustment for confounding factors. In summary, low serum CTRP3 is a strong predictor for the prevalence of NAFLD in Chinese patients with newly diagnosed T2DM.

Divergent relationship of circulating CTRP3 levels between obesity and gender: a cross-sectional study.

C1q TNF Related Protein 3 (CTRP3) is a novel adipose tissue derived secreted factor, or adipokine, which has been linked to a number of beneficial biological effects on metabolism, inflammation, and survival signaling in a variety of tissues. However, very little is known about CTRP3 in regards to human health. The purpose of this project was to examine circulating CTRP3 levels in a clinical population, patients with symptoms requiring heart catheterization in order to identify the presence of obstructive coronary artery disease (CAD). It was hypothesized that serum CTRP3 levels would be decreased in the presence of CAD.MethodsBody mass index (BMI), diabetes status, and plasma samples were collected from 100 patients who were >30 years of age and presented at the East Tennessee State University Heart Clinic with symptoms requiring heart catheterization in order to identify the presence of cardiovascular blockages (n = 52 male, n = 48 female). Circulating CTRP3 levels were quantified using commercially available ELISA.ResultsCirculating CTRP3 levels had no relationship to the presence of CAD regardless of gender. However, circulating concentrations of CTRP3 were significantly higher in normal weight (BMI < 30) females (0.88 ± 0.12 µg/ml) compared with males (0.54 ± 0.06 µg/ml). Further, obesity (BMI > 30) resulted in an increase in circulating CTRP3 levels in male subjects (0.74 ± 0.08 µg/ml) but showed a significant decrease in female subjects (0.58 ± 0.07 µg/ml). Additionally, there was a significant reduction in circulating CTRP3 levels in female subjects who were diagnosed with Type 2 diabetes compared with patients without (0.79 ± 0.08 vs. 0.42 ± 0.10 µg/ml). There was no relationship between diabetes status and circulating CTRP3 levels in male subjects.ConclusionCirculating CTRP3 levels had a different relationship with diabetes and obesity status between male and female patients. It is possible that circulating CTRP3 levels are controlled by hormonal status, however more research is needed to explore this relationship. Nevertheless, future studies examining the relationship between CTRP3 levels and disease status should treat gender as an independent variable.

CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function.

Endothelial dysfunction and inflammation are believed to be 2 primary instigators of pulmonary arterial hypertension (PH). C1q/TNF-related protein 9 (CTRP9) plays important roles in anti-inflammation and improvement of epithelial function. However, the role of CTRP9 in the progression of PH remains still unclear. In this study, the role and mechanism of CTRP9 in the PH progression were explored. First, serum CTRP9 contents and CTRP9 mRNA expression in the pulmonary artery epithelial cells from patients with PH were detected. Our data on enzyme-linked immunosorbent assay and real-time quantitative Polymerase Chain Reaction showed that CTRP9 mRNA and protein content were markedly downregulated in the patients with PH. Then the pcDNA-CTRP9 expression vector or CTRP9 siRNA was transfected into the primary pulmonary artery epithelial cells from the patients with PH in vitro. CTRP9 overexpression significantly improved endothelial NOS protein expression and reduced the secretion of endothelin-1 (ET-1) and matrix metalloproteinase-2 (MMP-2), whereas knockdown of CTRP9 sharply reduced eNOS protein expression and promoted the secretion of ET-1 and MMP-2 in the cultured human epithelial cells. Moreover, the levels of phosphatidylinositol 3-kinase (PI3K) and pAkt were reduced in the epithelial cells and CTRP9 overexpression activated the PI3K/Akt pathway. CTRP9 could inhibit cell apoptosis and eNOS expression reduction in the cells pretreated with the PI3K/Akt inhibitor LY294002 and resist LY294002-induced ET-1 and MMP-2 secretion. Finally, to verify the role of CTRP9 in the progression of PH in vivo, the pcDNA-CTRP9 expression vector or CTRP9 siRNA was intravenously injected into rats with PH. Pulmonary arterial pressures of the rats were notably reduced by the pcDNA-CTRP9 injection and elevated by the CTRP9 siRNA injection. In conclusion, CTRP9 ameliorated PH by attenuating inflammation and improving endothelial cell survival and function.

C1q/TNF-Related Protein-9 (CTRP9) Levels Are Associated With Obesity and Decrease Following Weight Loss Surgery.

C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has beneficial metabolic and cardiovascular effects in various animal models. Alterations in circulating CTRP9 have also been observed in patients with cardiovascular disease and diabetes, but little is known about the impact of obesity and bariatric surgery on CTRP9 concentrations. The aim of this study was to compare CTRP9 levels in obese and lean subjects and to determine whether circulating CTRP9 levels in morbidly obese patients are altered by bariatric surgery. Fifty-nine obese bariatric surgical patients and 62 lean controls were recruited to participate in a cross-sectional study at an academic medical center. The obese patients were further invited to participate in a cohort study, and 21 returned for analysis at 3 and 6 months postsurgery. Bariatric surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy) was the intervention for this study. Fasting serum was obtained from all subjects on entry to the study and was analyzed in the core laboratory for hemoglobin A1c, glucose, aspartate aminotransferase, alanine aminotransferase, total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides; CTRP9, insulin, adiponectin, and leptin were measured by ELISA. Serum from the patients in the cohort study was also analyzed at 3 and 6 months. Serum CTRP9 was significantly higher in the obese group compared to the lean group. CTRP9 was associated with obesity, even after controlling for age, gender, and ethnicity. Following bariatric surgery, there was a significant decrease in weight at 3 and 6 months postprocedure, accompanied by decreases in CTRP9, hemoglobin A1c and leptin, and an increase in serum adiponectin. CTRP9 levels are elevated in obesity and significantly decrease following weight loss surgery. Our data suggest that CTRP9 may play a compensatory role in obesity, similar to that of insulin, and is down-regulated following weight loss surgery.

Serum C1q/TNF-related protein-3 (CTRP3) levels are decreased in obesity and hypertension and are negatively correlated with parameters of insulin resistance.

BackgroundInsulin resistance (IR) correlates closely with cardiovascular disease. C1q/TNF-related protein-3 (CTRP3) is a novel adipokine that modulates insulin activity in various diseases. This study investigated the relationship between CTRP3 and IR as well as systemic inflammation in newly diagnosed obese and hypertensive patients (NCT02226471).MethodsSerum CTRP3 levels, anthropometric, inflammatory and metabolic parameters were measured in 180 obesity and essential hypertensive patients and in 66 normal weight, normotensive subjects.ResultsThe serum CTRP3 levels in the obesity group were lower than those in the NW group; these levels were also lower in hypertensive subjects than in normotensive subjects. After adjusting for gender, systolic blood pressure (SBP) and diastolic blood pressure (DBP), a modestly linear relationship was observed between CTRP3 and waist circumference (WC) (r = -0.168, p = 0.009), waist-to-hip ratio (WHR) (r = -0.183, p = 0.004), homeostasis model assessment of IR (HOMA-IR) (r = -0.264, p = 0.000), triglycerides (TG) (r = -0.136, p = 0.034), fasting blood glucose (FBG) (r = -0.155, p = 0.016), fasting insulin (FINS) (r = -0.248, p = 0.000) and homeostasis model assessment of β-cell insulin secretion (HOMA-β) (r = -0.128, p = 0.047). Multiple stepwise regression analysis revealed that gender, DBP and HOMA-IR were independently associated with serum CTRP3 levels.ConclusionCTRP3 was an independent factor affecting blood pressure and IR, and may play an important role in the pathogenesis of obesity and hypertension.

Association of serum C1q/TNF-related protein-9 concentration with arterial stiffness in subjects with type 2 diabetes.

Although recent animal studies have suggested that C1q/TNF-related protein-9 (CTRP9) is more likely to be involved in the regulation of vascular function, more specifically atherosclerosis, in rodents, little is known about whether serum CTRP9 level is associated with atherosclerosis in humans. The aim of this study was to investigate whether serum CTRP9 concentration is associated with atherosclerosis by measuring brachial ankle pulse wave velocity (baPWV) in subjects with type 2 diabetes. In addition, we examined the clinical and biochemical variables associated with serum CTRP9 concentration. We measured circulating CTRP9 and total adiponectin levels in 278 subjects (169 men and 109 women; mean age of 58.3 years) with type 2 diabetes. Measurements of baPWV were performed in all subjects. Serum CTRP9 concentration was positively correlated with baPWV. This correlation was significant even after adjusting for total adiponectin levels. In multiple linear regression, serum CTRP9 concentration was independently associated with increased baPWV. Female gender, higher body mass index, and homeostatic model assessment of insulin resistance were significantly associated with elevated serum CTRP9 concentration in subjects with type 2 diabetes. Serum CTRP9 concentration was significantly and positively associated with arterial stiffness in patients with type 2 diabetes, suggesting that CTRP9 might be important in the regulation of arterial stiffness in humans.

Association of serum C1q/TNF-Related Protein-9 (CTRP9) concentration with visceral adiposity and metabolic syndrome in humans

C1q/TNF-Related Protein (CTRP) family members are novel adipokines that have anti-inflammatory, immunomodulatory, glucose-regulating and vascular effects. However, the metabolic effects of CTRP9 remain unclear in humans. The aims of this study were to investigate whether serum CTRP9 concentrations are associated with glucose tolerance, metabolic parameters and abdominal fat accumulation. In addition, the authors investigated whether the aforementioned effects of CTRP9 are independent of serum adiponectin levels. A total of 221 subjects (140 men and 81 women), 25-72 years of age (mean age 46.0 years), were randomly selected from two different study populations. The normal glucose tolerance group (n=120) was selected from one study population and the prediabetes/type 2 diabetes group (n=101) was selected from the other study population. Serum CTRP9, total adiponectin concentrations and abdominal fat via computed tomography scan were measured in all subjects. Subjects in the lower serum CTRP9 tertile were older, had metabolically unhealthy profiles and had lower serum total adiponectin levels when compared with subjects in the middle or upper serum CTRP9 tertiles. In addition, serum CTRP9 concentration were inversely correlated with age, blood pressure, fasting glucose, homeostasis model assessment for insulin resistance, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels (all P<0.01) and positively correlated with serum total adiponectin levels (P=0.03). In terms of abdominal fat accumulation, serum CTRP9 concentrations were inversely correlated with visceral fat amount (P<0.01), but no correlation was observed with subcutaneous fat amount. Finally, serum CTRP9 was inversely associated with the presence of metabolic syndrome, independent of age, sex, body mass index, smoking status, total cholesterol, visceral fat and serum total adiponectin concentrations (odds ratio per 1 s.d. 0.47; 95% confidence interval 0.32-0.70; P<0.01). Serum CTRP9 concentrations were positively associated with favorable glucose or metabolic phenotypes and absence of metabolic syndrome, independent of serum total adiponectin concentrations.