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

Abstract

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 C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 Serum Levels with Coronary Artery Disease in Subjects with and without Type 2 Diabetes Mellitus

“…Based on multivariate linear regression analysis, BMI and smoking appear to be negative predictors of the CTRP3 serum levels. Compatible with a previous study in obese patients [11,16] our finding is a further evidence linking obesity to CTRP3. It has been reported that cigarette decreases expression of PPAR-γ [35] and the CTRP3 promoter has a PPAR response element [20], hence it seems likely that negative association of smoking and CTRP3 may be a result of cigarette effect on PPAR-γ expression.…”

“…CTRP3 also reduced gluconeogenesis and subsequent glucose output in hepatocytes [9]. Also, this adipokine has cardio-protective properties [10] and its circulating levels drop in obesity and individuals with high blood pressure, and is inversely associated with insulin resistance parameters [11]. This protein was found to inhibit inflammation and improve insulin sensitivity in 3T3-L1 adipocytes [12].…”

CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

“…In light of the myriad functions demonstrated for CTRP3 based on recombinant protein supplementation and overexpression in rodents, our current loss-of-function studies using Ctrp3-KO mice help provide critical insights into the functional significance of this secreted plasma protein that exhibits reduced circulating levels in rodent models of obesity and diabetes (29,42) as well as in obese and diabetic humans (3,9,63,71). Based on our previous studies using recombinant protein infusion and transgenic overexpression in mice (40,42), we expected the Ctrp3-KO mice to exhibit impaired energy balance.…”

“…Functional insights gained from multiple rodent models have prompted recent investigations of CTRP3 plasma levels in humans; however, conflicting results have been reported for its association with diabetes and the metabolic syndrome (3,8,63,71). The first study showed elevated CTRP3 levels in patients with type 2 diabetes (8), whereas subsequent studies reported lower levels of CTRP3 in individuals with metabolic syndrome (71), newly diagnosed patients with type 2 diabetes (3), obesity (63), or obese patients with hypertension and insulin resistance (9). Furthermore, women with polycystic ovarian syndrome were also found to have lower circulating CTRP3 levels compared with their matched controls, and metformin treatment was found to increase CTRP3 serum levels (54).…”

Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease

“…Recent studies demonstrate that, like adiponectin, some CTRPs act as adipokines that exert cardioprotective effects. Examples include CTRP3 and CTRP9, which are primarily expressed in adipose tissue and whose expression is downregulated in obese states 316–319 .…”