Complement activation in obesity, insulin resistance, and type 2 diabetes mellitus

Table 1 The roles of complement proteins in obesity, insulin resistance, diabetes

Complement protein	Obesity	Insulin resistance	Diabetes
C3	Increases adipose tissue inflammation[45,46]; Highly expressed in adipose tissue[70,71]	Marker of insulin resistance[42]	Proinflammatory cytokine causing systemic low-grade inflammation, insulin resistance and impaired glucose uptake[67-69]; Link between inflammation and thrombosis[75,76]; Higher concentrations associated with increased risk of diabetic complications[86]
C3a and C3aR	Increased levels of C3 in obese individuals[43,47,48]; Increased C3aR in white adipose tissue[49]	Improved glucose tolerance and insulin resistance in C3aR-/- mice[54,55,84]	Proinflammatory cytokine enhanced by cross-talk with TLR4 and C3[45,46]; C3a augments insulin secretion from mouse pancreatic beta cells[83]
C3adesArg (ASP)	Increased levels found in obese individuals[14,53]; Obesity induced adipose tissue creates this product leading to a pro-inflammatory state and ASP resistance[55]	Insulin-like properties by stimulating uptake of glucose and synthesis of triglycerides in adipose tissue[55]	Stimulating glucose uptake and lipid storage in adipose tissue[70,71]; Plays a role in chronic inflammation and contribute to microvascular complications[87]
C5a and C5aR	Expressed in adipocytes[49]; Play role in adipose tissue biology and development of metabolic disorders		Affect coagulation and contribute to inflammation[22-27]
Factor I and H	Increased in adipose tissue, activated by complement activation and affecting adipose tissue biology[41,42]
sC5b-9 and MASP-2			Elevated in T2DM; Contributing to endothelial dysfunction and ROS production in diabetes pathophysiology[62,95-97]; MASP-2 contributes to complications of diabetes[94]
CD 59 and MAC			Decreased levels of CD 59 in diabetics[62]; Increased levels of MAC found in diabetic patients and contributes to pathophysiology of complications[62,95-97]

MAC: Membrane attack complex; ROS: Reactive oxygen species; MASP: Mannan-binding lectin-associated serine proteases; ASP: Acylation stimulating factor; T2DM: Type 2 diabetes mellitus; TLR: Toll-like receptors.