C1q/TNF-related Protein-3 Research Articles

Effects of the new adiponectin paralogous protein CTRP-3 and of LPS on cytokine release from monocytes of patients with type 2 diabetes mellitus

Aims/Hypothesis: It was the aim to investigate the hypothesis that the new C1q/TNF-family member CTRP-3 (C1q/TNF-related protein-3) acts anti-inflammatory in human monocytes from healthy controls and patients with type 2 diabetes mellitus (T2D). Methods: Monocytes were isolated from 20 healthy controls and 30 patients with T2D. IL-6 and TNF concentrations were measured by ELISA. CTRP-3 was expressed in insect cells and used for stimulation experiments. Results: Basal IL-6 and TNF were not different in control and in T2D monocytes. LPS-stimulation (1 μg/ml) significantly ( p < 0.001) increased IL-6 and TNF in the supernatants of control and in T2D monocytes to a similar extent. CTRP-3 (1 μg/ml) significantly ( p = 0.03) inhibited LPS-induced IL-6 in control monocytes but not in T2D monocytes. TNF upon co-stimulation with LPS and CTRP-3 was significantly ( p = 0.012) lower in control than in T2D monocytes. LPS-induced TNF concentration was significantly and positively correlated with serum total cholesterol and LDL cholesterol in T2D patients. Conclusions: CTRP-3 inhibits LPS-induced IL-6 and TNF release. This anti-inflammatory effect is lost in T2D. Serum cholesterol concentration affects the pro-inflammatory potential of LPS to induce TNF release from T2D monocytes in the presence or absence of CTRP-3. CTRP-3 might partly account for the pro-inflammatory state in T2D.

Effects of the New C1q/TNF‐related Protein (CTRP‐3) “Cartonectin” on the Adipocytic Secretion of Adipokines

Cartonectin (collagenous repeat-containing sequence of 26-kDa protein; CORS-26) was described as a new adipokine of the C1q/TNF molecular superfamily C1q/TNF-related protein-3 (CTRP-3), secreted by the adipocytes of mice and humans. The receptor and function of cartonectin are unknown and the recombinant protein is not commercially available. To investigate the effects of recombinant cartonectin on the secretion of adipokines such as adiponectin, leptin, and resistin from adipocytes of human and murine origin. The effect of the BMI of the adipocyte donor was also investigated. Human adipocytes from pooled lean and preobese healthy individuals and murine 3T3-L1 adipocytes were used for stimulation experiments. Recombinant cartonectin was expressed in insect H5 cells. Adipokine secretion was measured using enzyme-linked immunosorbent assay. In addition, western blot analysis and luciferase reporter gene assays were employed. Cartonectin (1, 10, 50, and 250 ng/ml) in higher doses stimulates the secretion of adiponectin and resistin from murine adipocytes. This effect is not caused by an induction of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) protein expression, as confirmed by western blot analysis. Also, luciferase reporter gene assay revealed that cartonectin failed to induce luciferase activity at the peroxisome proliferator-activated receptor responsive element site containing the adiponectin/luciferase promoter fragment. Human adipocytes from lean individuals secrete higher amounts of adiponectin and leptin when compared with adipocytes of individuals with a preobesity BMI (25-30 kg/m(2)). Cartonectin failed to stimulate adiponectin or leptin secretion from human adipocytes, irrespective of the BMI value. Cartonectin is a new adipokine that differentially regulates the secretion of classical adipokines, with marked differences between the human and the murine systems. These effects are species-dependent, while basal adipokine secretion is influenced by the BMI.

Adiponectin and Coronary Heart Disease: The Strong Heart Study

To the Editor: The adipocyte secreted protein, adiponectin, is of particular interest in metabolic and vascular disease because of its close associations with insulin sensitivity and obesity.1 Lower levels of adiponectin are associated with later development of type 2 diabetes.2 Recent observations from the Health Professionals Follow-Up Study3 suggest that lower adiponectin concentrations might also be associated with incident myocardial infarction, findings in keeping with prior observations in patients with end-stage renal failure.4 We examined prospective relationships of adiponectin to vascular disease in a case–control series selected from the Strong Heart Study (SHS). The SHS is the largest study of cardiovascular disease in American Indians, a group at particular risk of obesity and type 2 diabetes and in whom an increasing incidence of coronary heart disease (CHD) is seen.5 Cases and controls were selected from the SHS cohort.6 The SHS recruited 4549 volunteers of American Indian heritage from 3 geographic areas (Arizona, North and South Dakota, and Oklahoma).6 Volunteers (59% female) were invited to a study examination on three occasions (SH1, 1988 to 1992; SH2, 1993 to 1995; SH3, 1997 to 1999) and remained under continued surveillance for development of vascular disease as described previously.7,8 Because of availability of plasma samples, baseline data for this study were taken from the second examination (SH2), and participants with prevalent cardiovascular disease at SH2 (definite CHD and stroke), …