Complement Components, C3 and C4, and the Metabolic Syndrome

2018 ◽  
Vol 15 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Melanie Copenhaver ◽  
Chack-Yung Yu ◽  
Robert P. Hoffman
Keyword(s):  
Metabolic Syndrome ◽  
Significant Role ◽  
Complement System ◽  
Gene Copy ◽  
Future Research ◽  
Obese Adults ◽  
Complement Components ◽  
Cardiometabolic Diseases ◽  
The Metabolic Syndrome ◽  
The Complement System

Introduction: Increased systemic inflammation plays a significant role in the development of adult cardiometabolic diseases such as insulin resistance, dyslipidemia, atherosclerosis, and hypertension. The complement system is a part of the innate immune system and plays a key role in the regulation of inflammation. Of particular importance is the activation of complement components C3 and C4. C3 is produced primarily by the liver but is also produced in adipocytes, macrophages and endothelial cells, all of which are present in adipose tissues. Dietary fat and chylomicrons stimulate C3 production. Adipocytes in addition to producing C3 also have receptors for activated C3 and other complement components and thus also respond to as well as produce a target for complement. C3adesArg, also known as acylation stimulation factor, increases adipocyte triglyceride synthesis and release. These physiological effects play a significant role in the development of metabolic syndrome. Epidemiologically, obese adults and non-obese adults with cardiometabolic disease who are not obese have been shown to have increased complement levels. C4 levels also correlate with body mass index. Genetically, specific C3 polymorphisms have been shown to predict future cardiovascular events and. D decreased C4 long gene copy number is associated with increased longevity. Conclusion: Future research is clearly needed to clarify the role of complement in the development of cardiovascular disease and mechanisms for its action. The complement system may provide a new area for intervention in the prevention of cardiometabolic diseases.

scholarly journals A screening test for determining the functional activity of the complement system classic pathway

2018 ◽  
pp. 134-137
Author(s):  
Б.Б. Шойбонов ◽  
О.М. Драпкина ◽  
С.О. Елиашевич ◽  
А.А. Федорович ◽  
Е.А. Лавренова ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Complement System ◽  
Functional Activity ◽  
Screening Test ◽  
The Metabolic Syndrome ◽  
High Degree ◽  
The Complement System ◽  
Simple Screening ◽  
Commercial Kit ◽  
Classic Pathway

Цель настоящей работы - разработка доступного теста для скрининга функциональной активности системы комплемента по классическому пути. Материалы и методы. В работе исследовали сыворотки крови 90 относительно здоровых лиц с избыточной массой тела (ИМТ >25) без метаболического синдрома. Иммуноферментный анализ функциональной активности системы комплемента по классическому пути проводили с использованием коммерческого набора. Реакцию лизиса эритроцитов барана, сенсибилизированных антителами (ЕА), оценивали турбидиметрически по снижению оптической плотности суспензии при длине волны 620 нм, степень лизиса определяли по калибровочному графику. Результаты. Разработан простой скрининг-тест для определения функциональной активности классического пути системы комплемента. Корреляционный анализ показал высокую степень сходимости результатов (r = 0,496), полученных разными методами. Заключение. Скрининг-тест для определения функциональной активности классического пути системы комплемента является быстрым, информативным и доступным для рутинных исследований. The aim of this work was to develop an accessible test for screening the functional activity of the complement system classic pathway. Materials and methods. Blood serum from 90 relatively healthy, overweight (BMI>25) individuals without the metabolic syndrome was studied. Enzyme immunoassay of the complement system functional activity following the classic pathway was performed using a commercial kit. The lysis of antibody-sensitized sheep erythrocytes was evaluated turbidimetrically by a decrease in suspension optical density at a wavelength of 620 nm; the lysis intensity was determined by the calibration curve. Results. A simple screening test was developed to determine the functional activity of the complement classic pathway. A high degree of correlation (r = 0.496) was observed between results obtained by different methods. This screening test for evaluating the functional activity of classic complement system pathway is fast, informative, and available for routine research.

Anti-Inflammatory Effects of Exercise on Metabolic Syndrome Patients: A Systematic Review and Meta-Analysis

2020 ◽  
pp. 109980042095806 ◽  
Author(s):  
Heidar Alizaei Yousefabadi ◽  
Arghavan Niyazi ◽  
Sahar Alaee ◽  
Mehrdad Fathi ◽  
Gholam Rasul Mohammad Rahimi
Keyword(s):  
Metabolic Syndrome ◽  
Exercise Training ◽  
Inflammatory Markers ◽  
Meta Analysis ◽  
Serum Levels ◽  
Future Research ◽  
The Metabolic Syndrome ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Training Impact

Background: Increments in inflammatory indicators and low levels of physical activity are correlated to the expansion of the metabolic syndrome (MetS). Objective: The purpose of this study was to establish if exercise training ameliorates inflammatory status in MetS patients. Data sources: PubMed, CINAHL, and Medline, Google Scholar, and Scopus databases and reference lists of included studies were searched. Study selection: Twenty randomized controlled trials (RCTs) of exercise-training impact on inflammatory markers (tumor necrosis factor (TNF) α, C-reactive protein (CRP), interleukin (IL) 6, IL-8, IL-10, and IL-18) with concurrent control groups were included in this analysis. Results: Results demonstrated an overall significant decrease in serum levels of TNF-α (mean difference (MD): −1.21 pg/ml; 95% confidence interval (CI): −1.77, −0.66), CRP (MD: −0.52 mg/l; 95% CI: −0.79, −0.25), IL-8 (MD: −1.31 pg/ml; 95% CI: −2.57, −0.06), and a significant increase in IL-10 (MD: 0.48 pg/ml; 95% CI: 0.10, 0.86). But exercise training did not change the level of IL-6 (MD: −0.69 pg/ml; 95% CI: −1.53, 0.14) and IL-18 (MD: −53.01 pg/ml; 95% CI: −166.64, 60.62). Conclusion: Exercise training improves TNF-α, CRP, IL-8, and IL-10 levels in patients with MetS. For some variables, isolated aerobic exercise, and combined aerobic and resistance exercise appears to be optimal. Future research is needed to clarify the mechanisms underlying exercise training’s effect on this population’s inflammatory markers. More studies are required to confirm these findings.

scholarly journals Development of a Novel Cytomedical Treatment that can Protect Entrapped Cells from Host Humoral Immunity

2002 ◽  
Vol 11 (8) ◽  
pp. 787-797 ◽  
Author(s):  
Ryo Suzuki ◽  
Yasuo Yoshioka ◽  
Etsuko Kitano ◽  
Tatsunobu Yoshioka ◽  
Hiroaki Oka ◽  
...  
Keyword(s):  
Humoral Immunity ◽  
Complement System ◽  
Alternative Pathway ◽  
Classical Pathway ◽  
Dependent Manner ◽  
Complement Components ◽  
Alternative Pathways ◽  
Low Cytotoxicity ◽  
The Complement System

Cell therapy is expected to relieve the shortage of donors needed for organ transplantation. When patients are treated with allogeneic or xenogeneic cells, it is necessary to develop a means by which to isolate administered cells from an immune attack by the host. We have developed “cytomedicine, ” which consists of functional cells entrapped in semipermeable polymer, and previously reported that alginate-poly-l-lysine-alginate microcapsules and agarose microbeads could protect the entrapped cells from injury by cellular immunity. However, their ability to isolate from humoral immunity was insufficient. It is well known that the complement system plays an essential role in rejection of transplanted cells by host humoral immunity. Therefore, the goal of the present study was to develop a novel cytomedical device containing a polymer capable of inactivating complement. In the screening of various polymers, polyvinyl sulfate (PVS) exhibited high anticomplement activity and low cytotoxicity. Murine pancreatic β-cell line (MIN6 cell) entrapped in agarose microbeads containing PVS maintained viability and physiological insulin secretion, replying in response to glucose concentration, and resisted rabbit antisera in vitro. PVS inhibited hemolysis of sensitized sheep erythrocytes (EAs) and rabbit erythrocytes by the complement system. This result suggests that PVS inhibits both the classical and alternative complement pathways of the complement system. Next, the manner in which PVS exerts its effects on complement components was examined. PVS was found to inhibit generation of C4a and Ba generation in activation of the classical and alternative pathways, respectively. Moreover, when the EAC1 cells, which were carrying C1 on the EAs, treated with PVS were exposed to C1-deficient serum, hemolysis decreased in a PVS dose-dependent manner. These results suggest that PVS inhibits C1 in the classical pathway and C3 convertase formation in the alternative pathway. Therefore, PVS may be a useful polymer for developing an anticomplement device for cytomedical therapy.

scholarly journals Effects of Exercise Training Intensity on Nocturnal Growth Hormone Secretion in Obese Adults with the Metabolic Syndrome

2009 ◽  
Vol 94 (6) ◽  
pp. 1979-1986 ◽  
Author(s):  
Brian A. Irving ◽  
J. Y. Weltman ◽  
James T. Patrie ◽  
Christopher K. Davis ◽  
David W. Brock ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Growth Hormone ◽  
Exercise Training ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Training Intensity ◽  
Obese Adults ◽  
The Metabolic Syndrome

Pre- and early postnatal nongenetic determinants of type 2 diabetes

2002 ◽  
Vol 4 (24) ◽  
pp. 1-14 ◽  
Author(s):  
Susan E. Ozanne ◽  
C. Nick Hales
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Hormone Receptors ◽  
Early Growth ◽  
Growth Restriction ◽  
Future Research ◽  
Thrifty Phenotype ◽  
The Metabolic Syndrome

Epidemiological studies have revealed strong and internationally reproducible links between early growth restriction and subsequent risk of developing type 2 diabetes and the metabolic syndrome (glucose intolerance, hypertension and hypertriglyceridaemia). This effect can exist independently of genetic factors. There is also direct evidence that poor maternal nutrition and maternal smoking cause both a reduction in birthweight and subsequent loss of glucose tolerance. High rates of growth in childhood may add to these effects. The ‘thrifty phenotype’ hypothesis attempts to explain these associations in terms of an altered programming of growth and metabolism that aids survival both pre- and postnatally. Type 2 diabetes is envisaged as a consequence of a clash of this programming with adult obesity. Tests of this hypothesis in animal models have shown that both the metabolic syndrome and type 2 diabetes can result from early growth restriction in rats consequent upon rat dams being fed a reduced protein, isocaloric diet (in which the protein is replaced by an equal quantity of nonprotein energy). A variety of other models of early growth restriction in rats lead to a similar phenotype. Several structural and gene expression changes have been shown in many tissues, including pancreas, liver, kidney, muscle and adipose tissue. Changes in gene expression include those concerned with hormone receptors, signalling and glycolytic enzymes. Many important questions remain for future research.

Introduction to the complement system

1984 ◽  
Vol 306 (1129) ◽  
pp. 279-281 ◽  
Keyword(s):  
Humoral Immunity ◽  
Complement System ◽  
Bacterial Infections ◽  
Cross Linking ◽  
Complement Components ◽  
The Third ◽  
Effector Mechanism ◽  
The Complement System

Complement is the essential effector mechanism in humoral immunity to infection. Combination of antibody with antigen causes cross-linking, leading to precipitation of soluble antigens and agglutination of particular antigens, but no more. Unless complement is also present, agglutinated microorganisms can, in appropriate media in vitro grow out and form as lethal a culture as if not reacted with antibody. That this is also true in vivo is apparent from experience with patients with inherited deficiencies in complement components. The pattern is complex because of the presence of two pathways of activation, but in the rare cases of deficiency of the third component, C3, which is central to both pathways, the individuals are susceptible to repeated bacterial infections similar to aggammaglobulinaemics who are unable to synthesize antibodies. Both antibodies and complement are essential for effective humoral immunity.

Solution structures of complement components by X-ray and neutron scattering and analytical ultracentrifugation

2002 ◽  
Vol 30 (6) ◽  
pp. 996-1001 ◽  
Author(s):  
S. J. Perkins ◽  
H. E. Gilbert ◽  
M. Aslam ◽  
J. Hannan ◽  
V. M. Holers ◽  
...  
Keyword(s):  
Neutron Scattering ◽  
Complement System ◽  
Analytical Ultracentrifugation ◽  
Factor H ◽  
Protein Domain ◽  
Complement Receptor ◽  
Complement Components ◽  
X Ray ◽  
Solution Studies ◽  
The Complement System

The short consensus/complement repeat (SCR) domain (also known as the complement control protein domain) is the most abundant domain type in the complement system. Crystal and NMR structures for proteins that contain single and multiple SCR domains have now been published. These contain inter-SCR linkers of between three and eight residues, and the structures show much variability in inter-SCR orientations. X-ray and neutron scattering, combined with analytical ultracentrifugation and constrained modelling based on known subunit structures will yield a medium-resolution structure for the protein of interest. The fewer parameters that are associated with the structure of interest, the more defined the structure of interest becomes. These solution studies have been applied to several SCR-containing proteins in the complement system, most notably Factor H with 20 SCR domains, a complement receptor type 2 fragment with two SCR domains, and rat complement receptor-related protein (Crry) which contains five SCR domains. The results show great conformational variability in the inter-SCR orientation, and these will be reviewed. Even though the rotational orientation cannot be modelled, it is nonetheless possible to measure the degree of extension of the multi-SCR proteins and, from this, to obtain functionally useful results.

Metabolic syndrome and endothelial fibrinolytic capacity in obese adults

2008 ◽  
Vol 294 (1) ◽  
pp. R39-R44 ◽  
Author(s):  
Gary P. Van Guilder ◽  
Greta L. Hoetzer ◽  
Jared J. Greiner ◽  
Brian L. Stauffer ◽  
Christopher A. DeSouza
Keyword(s):  
Metabolic Syndrome ◽  
Defense Mechanism ◽  
Normal Weight ◽  
Tissue Type ◽  
Vascular Events ◽  
Obese Adults ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Artery Disease

The metabolic syndrome (MetS) often accompanies obesity and contributes to the increased risk of atherothrombotic events with increased body fatness. Indeed, the risks for coronary artery disease and acute vascular events are greater with obesity combined with MetS compared with obesity alone. Endothelial release of tissue-type plasminogen activator (t-PA) is a key defense mechanism against thrombosis and has been shown to be impaired with obesity. The aim of the present study was to determine whether the presence of MetS exacerbates endothelial fibrinolytic dysfunction in obese adults. Net endothelial release of t-PA was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside in 47 sedentary adults: 15 normal weight (age 57 ± 2 yr; body mass index 22.9 ± 0.5 kg/m2), 14 obese but otherwise healthy (55 ± 1 yr; 29.4 ± 0.3 kg/m2), and 18 obese with MetS (55 ± 2 yr; 32.3 ± 1 kg/m2). MetS was established according to National Cholesterol Education Program ATP III criteria. Net release of t-PA antigen to bradykinin was ∼50% lower ( P < 0.01) in the obese (from 2.5 ± 1.9 to 37.1 ± 5.3 ng·100 ml tissue−1·min−1) and obese with MetS (from 0.4 ± 0.8 to 32.5 ± 3.8 ng·100 ml tissue−1·min−1) compared with normal-weight (from 0.9 ± 1.0 to 74.3 ± 8.1 ng·100 ml tissue−1·min−1) subjects. However, there were no significant differences in the capacity of the endothelium to release t-PA in the obese and obese with MetS adults. These results indicate that the presence of the MetS does not worsen the obesity-related endothelial fibrinolytic dysfunction.

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