The Role of Complement System in Adipose Tissue-related Inflammation

Overview

Journal Immunol Res

Specialty Allergy & Immunology

Date 2016 Jan 13

PMID 26754764

Citations 48

Authors

Sonia I Vlaicu

Alexandru Tatomir

Dallas Boodhoo

Stefan Vesa

Petru A Mircea

Horea Rus

Affiliations

Soon will be listed here.

Abstract

As the common factor linking adipose tissue to the metabolic context of obesity, insulin resistance and atherosclerosis are associated with a low-grade chronic inflammatory status, to which the complement system is an important contributor. Adipose tissue synthesizes complement proteins and is a target of complement activation. C3a-desArg/acylation-stimulating protein stimulates lipogenesis and affects lipid metabolism. The C3a receptor and C5aR are involved in the development of adipocytes' insulin resistance through macrophage infiltration and the activation of adipose tissue. The terminal complement pathway has been found to be instrumental in promoting hyperglycemia-associated tissue damage, which is characteristic of the major vascular complications of diabetes mellitus and diabetic ketoacidosis. As a mediator of the effects of the terminal complement complex C5b-9, RGC-32 has an impact on energy expenditure as well as lipid and glucose metabolic homeostasis. All of this evidence, taken together, indicates an important role for complement activation in metabolic diseases.

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References

Niculescu F, Niculescu T, Rus H . C5b-9 terminal complement complex assembly on apoptotic cells in human arterial wall with atherosclerosis. Exp Mol Pathol. 2004; 76(1):17-23. DOI: 10.1016/j.yexmp.2003.10.002. View

Podack E, Tschopp J . Polymerization of the ninth component of complement (C9): formation of poly(C9) with a tubular ultrastructure resembling the membrane attack complex of complement. Proc Natl Acad Sci U S A. 1982; 79(2):574-8. PMC: 345787. DOI: 10.1073/pnas.79.2.574. View

Schadt E, Lamb J, Yang X, Zhu J, Edwards S, GuhaThakurta D . An integrative genomics approach to infer causal associations between gene expression and disease. Nat Genet. 2005; 37(7):710-7. PMC: 2841396. DOI: 10.1038/ng1589. View

Moreno-Navarrete J, Martinez-Barricarte R, Catalan V, Sabater M, Gomez-Ambrosi J, Ortega F . Complement factor H is expressed in adipose tissue in association with insulin resistance. Diabetes. 2009; 59(1):200-9. PMC: 2797922. DOI: 10.2337/db09-0700. View

Krus U, King B, Nagaraj V, Gandasi N, Sjolander J, Buda P . The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events. Cell Metab. 2014; 19(5):883-90. DOI: 10.1016/j.cmet.2014.03.001. View

WHITE R, Damm D, Hancock N, Rosen B, Lowell B, USHER P . Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. J Biol Chem. 1992; 267(13):9210-3. View

Guo S, Philbrick M, An X, Xu M, Wu J . Response gene to complement 32 (RGC-32) in endothelial cells is induced by glucose and helpful to maintain glucose homeostasis. Int J Clin Exp Med. 2014; 7(9):2541-9. PMC: 4211757. View

Wlazlo N, van Greevenbroek M, Ferreira I, Jansen E, Feskens E, van der Kallen C . Low-grade inflammation and insulin resistance independently explain substantial parts of the association between body fat and serum C3: the CODAM study. Metabolism. 2012; 61(12):1787-96. DOI: 10.1016/j.metabol.2012.05.015. View

Gerl V, Bohl J, Pitz S, Stoffelns B, Pfeiffer N, Bhakdi S . Extensive deposits of complement C3d and C5b-9 in the choriocapillaris of eyes of patients with diabetic retinopathy. Invest Ophthalmol Vis Sci. 2002; 43(4):1104-8. View

10.

Murray I, Sniderman A, Cianflone K . Enhanced triglyceride clearance with intraperitoneal human acylation stimulating protein in C57BL/6 mice. Am J Physiol. 1999; 277(3):E474-80. DOI: 10.1152/ajpendo.1999.277.3.E474. View

11.

Jenny L, Ajjan R, KING R, Thiel S, Schroeder V . Plasma levels of mannan-binding lectin-associated serine proteases MASP-1 and MASP-2 are elevated in type 1 diabetes and correlate with glycaemic control. Clin Exp Immunol. 2014; 180(2):227-32. PMC: 4408157. DOI: 10.1111/cei.12574. View

12.

Vasil K, Magro C . Cutaneous vascular deposition of C5b-9 and its role as a diagnostic adjunct in the setting of diabetes mellitus and porphyria cutanea tarda. J Am Acad Dermatol. 2006; 56(1):96-104. DOI: 10.1016/j.jaad.2006.05.013. View

13.

Dunkelberger J, Song W . Complement and its role in innate and adaptive immune responses. Cell Res. 2009; 20(1):34-50. DOI: 10.1038/cr.2009.139. View

14.

Phieler J, Chung K, Chatzigeorgiou A, Ameln A, Garcia-Martin R, Sprott D . The complement anaphylatoxin C5a receptor contributes to obese adipose tissue inflammation and insulin resistance. J Immunol. 2013; 191(8):4367-74. PMC: 3817864. DOI: 10.4049/jimmunol.1300038. View

15.

Murray I, Sniderman A, Cianflone K . Mice lacking acylation stimulating protein (ASP) have delayed postprandial triglyceride clearance. J Lipid Res. 1999; 40(9):1671-6. View

16.

Rosoklija G, Dwork A, Younger D, Karlikaya G, Latov N, Hays A . Local activation of the complement system in endoneurial microvessels of diabetic neuropathy. Acta Neuropathol. 2000; 99(1):55-62. DOI: 10.1007/pl00007406. View

17.

Engstrom G, Hedblad B, Eriksson K, Janzon L, Lindgarde F . Complement C3 is a risk factor for the development of diabetes: a population-based cohort study. Diabetes. 2005; 54(2):570-5. DOI: 10.2337/diabetes.54.2.570. View

18.

Onat A, Can G, Rezvani R, Cianflone K . Complement C3 and cleavage products in cardiometabolic risk. Clin Chim Acta. 2011; 412(13-14):1171-9. DOI: 10.1016/j.cca.2011.03.005. View

19.

Jerath R, Burek C, Hoffman W, Passmore G . Complement activation in diabetic ketoacidosis and its treatment. Clin Immunol. 2005; 116(1):11-7. DOI: 10.1016/j.clim.2005.03.004. View

20.

Tegla C, Cudrici C, Patel S, Trippe 3rd R, Rus V, Niculescu F . Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res. 2011; 51(1):45-60. PMC: 3732183. DOI: 10.1007/s12026-011-8239-5. View