The Role of High Concentration of Resistin in Endothelial Dysfunction Through Induction of Proinflammatory Cytokines Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-6 (IL-6) and Chemokin Monocyte Chemotactic Protein-1 (MCP-1)
Abstract
BACKGROUND: Many previous studies have reported that central obesity is related to inflammation and endothelial dysfunction. It has also been reported that resistin can induce proinflammatory cytokines TNF-α and IL-6, which can result in endothelial dysfunction, although the role of resistin in human remains unclear. The aim of this study was to assess the role of resistin in influencing the proinflammatory cytokines TNF-α, IL-6, and chemokin MCP-1 in nondiabetic, central obese individuals. Results of this study are hoped to be useful to make a strategy for early prevention of endothelial dysfunction especially in obese individuals.
METHOD: This was a cross-sectional study on 73 non diabetic obese male subjects (waist circumferences >90 cm). Resistin, hs-TNF-α, IL-6, MCP-1, VCAM-1 were assessed by ELISA. Statistical analysis was performed using SPSS for Windows v.11.5 with significance p<0.05. The correlations among biomarkers were assessed using Spearman’s Rho test.
RESULTS: The study results showed a significant correlation between resistin and TNF-α (r=0.274, p<0.005), and a significant correlation between TNF-α and IL-6 (r=0.430, p<0.001). It was found that high concentration of resistin caused the concentration of TNF-α , IL-6 and MCP-1 to increase, and affected the increase of VCAM-1 (p=0.0030), A significant correlation between waist circumference and inflammation (hsCRP, r=0.296, p<0.005; IL-6, r=0.374, p<0.001 and HOMA IR, r=0.331, p<0.001) was also found.
CONCLUSION: This study showed that the role of resistin in endothelial dysfunction occurred at a high concentration of resistin through induction of proinflammatory cytokines TNF-α, IL-6, and chemokin MCP-1. We suggest that inflammation in obesity starts with a positive feedback loop mechanism between resistin and TNF-α.
KEYWORDS: obesity, inflammation, adipocytokines, resistin, tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1, vascular cell adhesion molecule–1
Full Text:
PDFReferences
Asia Pasific Cohort Study Collaboration. The burden of overweight and obesity in the Asia-Pasific Region. Obes Rev. 2007; 8: 191-6, CrossRef.
Caballero AE. Endothelial dysfunction in obesity and insulin resistance: A road to diabetes and heart disease. Obes Res. 2003; 11: 1278-89, CrossRef.
Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation. 2003; 108: 2054-9, CrossRef.
Verma S, Li SH, Wang CH, Fedak PWM, Li RK, Weisel RD, et al. Resistin promotes endothelial activation. Further evidence of adipositokine-endothelial interaction. Circulation. 2003; 108: 736-40, CrossRef.
Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005; 115: 1111-9, CrossRef.
Lehrke M, Lazar MA. Inflamed about obesity. Nat Med. 2004; 10: 126-7, CrossRef.
Lehrke M, Reilly MP, Milington SC, Iqbal DJ, Lazar MA. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Medicine. 2004; 1: 161-8, CrossRef.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003; 112: 1821-30, CrossRef.
Gaillard S, Gaillard RC. Adipose tissues as an endocrine organ. Obesity and Metabolism. 2007; 3: 191-205, CrossRef.
Gong D, Yang R, Munir KM, Horenstein RB, Shuldiner AR. New progress in adipocytokine research. Curr Opin Endo Diab. 2003; 10: 115-21, CrossRef.
Avogaro A, de Kreutzenberg SV. Mechanisms of endothelial dysfunction in obesity. Clin Chim Acta. 2005; 360: 9-26, CrossRef.
Reilly PM, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation. 2005; 111: 932-9, CrossRef.
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001; 409: 307-12, CrossRef.
Rang ZY, Huang Q, Xu A, McLenithan JC, Eison JA, Shuldiner AR, et al. Comparative studies of resistin expression and phylogenomics in human and mouse. Biochem Biophys Res Commun. 2003; 310: 927-35, CrossRef.
Kunnari A, Ukkola O, Päivänsalo M, Kesäniemi A. High plasma resistin level is associated with enhanced hsCRP and leucocytes. J Clin Endocrinol Metab. 2006; CrossRef.
Bokarewa M, Nagaev I, Smith U, Tarkowski A. Resistin, an adipocytokine with potent proinflamatory properties. J Immunol. 2005; 174: 5789-95, CrossRef.
Chen YH, Lee MJ, Chang HH, Hung PF, Kao YH. 17 beta-estradiol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor, extracellularly regulated kinase, and CCAAT/enhancer binding protein-alpha pathways. Endocrinology. 2006; 147: 4496-504, CrossRef.
Bo S, Gambino R, Pagani A, Guidi S, Gentile L, Cassader M, et al. Relationships between human serum resistin, inflammatory markers and insulin resistance. Int J Obes. 2005; 29: 1315-20, CrossRef.
Stejskal D, Adamovská S, Bartek J, Juráková R, Prosková J. Resistin-concentrations in persons with type 2 diabetes mellitus and in individuals with acute inflammatory disease. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2003; 147: 63-9, CrossRef.
Wellen K, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest. 2003; 112: 1785-8, CrossRef.
Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation. 2006; 113: 1888-904, CrossRef.
Guzik TJ, Mangalat D, Korbut R. Adipocytokines-novel link between inflammation and vascular function? J Physiol Pharmacol. 2006; 57: 505-28, PMID.
Kim JA, Koh KK, Quon MJ. The union of vascular and metabolic actions of insulin in sickness and in health. Arterioscler Thromb Vasc Biol. 2005; 25: 889-91, CrossRef.
Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ. Human resistin stimulates the pro-inflammatory cytokines TNF-α and IL-12 inmacrophages by NF-κβ-dependent pathway. Biochem Biophys Res Commun. 2005; 334: 1092-101, CrossRef.
Winther MPJ de, Kanters E, Kraal G, Hofker MH. Nuclear factor κβ signalling in atherogenesis. Aterioscler Thromb Vasc Biol. 2005; 25: 904-14, CrossRef.
Charo IF, Taubman MB. Chemokines in the pathogenesis of vascular disease. Circ Res. 2004; 95: 858-66, CrossRef.
Fain JN, Madan AK. Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue. Int J Obesity. 2005; 29: 1299-307, CrossRef.
DOI: https://doi.org/10.18585/inabj.v1i2.90
Copyright (c) 2009 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
