High Expression of Complement Components in Omental Adipose Tissue in Obese Men

Abstract

Res. 2003;11:699-708. Objective: Accumulation of visceral fat is recognized as a predictor of obesity-related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. Research Methods and Procedures: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real-time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. Results: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue (ϳ2-, 4-, 17-, 10-, and 7-fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r ϭ 0.65 and p Ͻ 0.001 and r ϭ 0.52 and p Ͻ 0.001, respectively) and women (r ϭ 0.34 and p ϭ 0.023 and r ϭ 0.49 and p Ͻ 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r ϭ 0.36, p ϭ 0.015) and with both depots in women (visceral: r ϭ 0.58, p Ͻ 0.001; and subcutaneous: r ϭ 0.51, p Ͻ 0.001). Discussion: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra-abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.

Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study

“…Cross-sectional studies have shown that obesity is associated with elevated plasma levels of C3 [4,[6][7][8][9][10], but the causal and temporal relations of this association have been unclear. The present study showed that C3 was strongly associated both with weight at baseline and weight at follow-up.…”

“…The synthesis of these proteins increases in response to inflammation and infection, with a slower increase than the traditional acute-phase proteins [1][2][3]. Although hepatic production is the main source of these proteins, C3 and C4 are also expressed and secreted by other cells, for example, in adipose tissue [4,5].…”

“…Individuals who are overweight or obese generally have raised concentrations of C3 and C4 [4][5][6][7][8][9][10], and it has been reported that C3 levels decrease after weight loss [6,7]. The proteolytic fragment of C3, acylation-stimulating protein (ASP), is a paracrine metabolic factor that stimulates the uptake of glucose and fat storage in human adipose tissue [11][12][13][14].…”

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

“…C3 is the key protein of the complement cascade, and is abundantly present in plasma. In addition, C3 is found in the peritoneal fluid [8] as well as in subcutaneous and omental adipose tissue [9]. C3 is a contributor to the biomaterial-induced inflammation during blood contact [10], and recently C3 was demonstrated to be involved in the inflammatory host response against subcutaneous and intraperitoneally implanted…”

The entero-insular axis and adipose tissue-related factors in the prediction of weight gain in humans

“…65 C3 and Factor B are positively correlated with body weight and visceral fat, and decrease after weight loss 66,67 ASP secretion by the adipose tissue is increased after meals and stimulates TG synthesis and decreases nonesterified FA release in adipocytes. 65 Levels of plasma ASP have been positively correlated with obesity, percent body fat and with insulin resistance.…”