Circulating Levels of the Adipokines Monocyte Chemotactic Protein-4 (MCP-4), Macrophage Inflammatory Protein-1β (MIP-1β), and Eotaxin-3 in Severe Obesity and Following Bariatric Surgery

Abstract

The aim of the study was to investigate the involvement of the adipokines eotaxin-3, MIP-1β, and MCP-4 in obesity and related comorbidities and the modification of their circulating levels after bariatric surgery. Eighty severely obese subjects and 20 normal-weight controls were included in the study. Circulating levels of MCP-4, MIP-1β, and eotaxin-3, and the main clinical, biochemical, and instrumental parameters for the evaluation of cardiovascular and metabolic profile were determined in controls and in obese subjects at baseline and 10 months after surgery. Within the obese group at baseline, eotaxin-3 levels were higher in males than females and in smokers than non-smokers and showed a positive correlation with LDL-cholesterol, apolipoprotein B, and leptin. MIP-1β showed a positive correlation with age and leptin and a negative correlation with adiponectin and was an independent predictor of increased carotid artery intima-media thickness. MCP-4 levels were higher in obese subjects than controls and showed a positive correlation with body mass index, eotaxin-3, and MIP-1β. Bariatric surgery induced a marked decrease in all the 3 adipokines. MCP-4 is a novel biomarker of severe obesity and could have an indirect role in favoring sub-clinical atherosclerosis in obese patients by influencing the circulating levels of eotaxin-3 and MIP-1β, which are directly related to the main atherosclerosis markers and risk factors. The reduction of circulating levels of MCP-4, eotaxin-3, and MIP-1β could be one of the mechanisms by which bariatric surgery contributes to the reduction of cardiovascular risk in these patients.

Key words

chemokines - low-grade inflammation - atherosclerosis - laparoscopic sleeve gastrectomy

• References

• 1 Rubenstein AH. Obesity: a modern epidemic. Trans Am Clin Climatol Assoc 2005; 116: 103-113
• 2 Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011; 29: 415-445
• 3 Trayhurn P, Wood IS. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans 2005; 33: 1078-1081
• 4 Yao L, Herlea-Pana O, Heuser-Baker J, Chen Y, Barlic-Dicen J. Roles of the Chemokine system in development of obesity, insulin resistance, and cardiovascular disease. J. Immunol Res 2014; 1-11
• 5 Tourniaire F, Romier-Crouzet B, Lee JH, Marcotorchino J, Gouranton E, Salles J, Malezet C, Astier J, Darmon P, Blouin E, Walrand S, Ye J, Landrier JF. Chemokine expression in inflamed adipose tissue is mainly mediated by NF-κB. PLoS One 2013; 8: e66515
• 6 Vasudevan AR, Wu H, Xydakis AM, Jones PH, Smith EO, Sweeney JF, Corry DB, Ballantyne CM. Eotaxin and obesity. J Clin Endocrinol Metab 2006; 91: 256-261
• 7 Panee J. Monocyte chemoattractant protein 1 (MCP-1) in obesity and diabetes. Cytokine 2012; 60: 1-12
• 8 Alomar SY, Zaibi MS, Kępczyńska MA, Gentili A, Alkhuriji A, Mansour L, Dar JA, Trayhurn P. PCR array and protein array studies demonstrate that IL-1β (interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes. Arch Physiol Biochem 2015; 121: 187-193
• 9 Maury E, Ehala-Aleksejev K, Guiot Y, Detry R, Vandenhooft A, Brichard SM. Adipokines oversecreted by omental adipose tissue in human obesity. Am J Physiol Endocrinol Metab 2007; 293: E656-E665
• 10 Meijer K, de Vries M, Al-Lahham S, Bruinenberg M, Weening D, Dijkstra M, Kloosterhuis N, van der Leij RJ, van der Want H, Kroesen BJ, Vonk R, Rezaee F. Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages. PLoS One 2011; 6: e17154
• 11 Hashimoto I, Wada J, Hida A, Baba M, Miyatake N, Eguchi J, Shikata K, Makino H. Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects. Obesity 2006; 14: 799-811
• 12 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
• 13 Lupattelli G, De Vuono S, Boni M, Helou R, Raffaele Mannarino M, Rita Roscini A, Alaeddin A, Pirro M, Vaudo G. Insulin resistance and not BMI is the major determinant of early vascular impairment in patients with morbid obesity. J Atheroscler Thromb 2013; 20: 924-933
• 14 Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, Horuk R, Sparre-Ulrich AH, Locati M, Luster AD, Mantovani A, Matsushima K, Murphy PM, Nibbs R, Nomiyama H, Power CA, Proudfoot AE, Rosenkilde MM, Rot A, Sozzani S, Thelen M, Yoshie O, Zlotnik A. International union of pharmacology. LIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev 2013; 66: 1-79
• 15 Garcia-Zepeda EA, Combadiere C, Rothenberg ME, Sarafi MN, Lavigne F, Hamid Q, Murphy PM, Luster AD. Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3. J Immunol 1996; 157: 5613-5626
• 16 Bystry RS, Aluvihare V, Welch KA, Kallikourdis M, Betz AG. B cells and professional APCs recruit regulatory T cells via CCL4. Nat Immunol 2001; 2: 1126-1132
• 17 Chirumbolo S, Franceschetti G, Zoico E, Bambace C, Cominacini L, Zamboni M. LPS response pattern of inflammatory adipokines in an in vitro 3T3-L1 murine adipocyte model. Inflamm Res 2014; 63: 495-507
• 18 Holewijn S, den Heijer M, Swinkels DW, Stalenhoef AF, de Graaf J. Apolipoprotein B, non-HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk. J Intern Med 2010; 268: 567-577
• 19 O’Leary DH, Polak JF, Krommal RA, Manolio TA, Burke GL, Wolfson SK. For the Cardiovascular Health Study Collaborative research Group: Carotid intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999; 340: 14-22
• 20 Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction the Rotterdam Study. Circulation 1997; 6: 1432-1437
• 21 Chambless LE, Heiss G, Folsom AR, Rosamund W, Szklo M, Sharrett AR, Clegg LX. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol 1997; 146: 483-494
• 22 Beltowski J. Leptin and atherosclerosis. Atherosclerosis 2006; 189: 47-60
• 23 Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, Sattar N. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation 2001; 104: 3052-3056
• 24 Söderberg S, Ahrén B, Jansson JH, Johnson O, Hallmans G, Asplund K, Olsson T. Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999; 246: 409-418
• 25 Söderberg S, Stegmayr B, Stenlund H, Sjöström LG, Agren A, Johansson L, Weinehall L, Olsson T. Leptin, but not adiponectin, predicts stroke in males. J Intern Med 2004; 256: 128-136
• 26 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79-83
• 27 Shimabukuro M, Higa N, Asahi T, Oshiro Y, Takasu N, Tagawa T, Ueda S, Shimomura I, Funahashi T, Matsuzawa Y. Hypoadiponectinemia is closely linked to endothelial dysfunction in man. J Clin Endocrinol Metab 2003; 88: 3236-3240
• 28 Tan KC, Xu A, Chow WS, Lam MC, Ai VH, Tam S, Lam KS. Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab 2004; 89: 765-769
• 29 Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clin Chim Acta 2007; 380: 24-30
• 30 Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291: 1730-1737
• 31 Boisvert WA. Modulation of atherogenesis by chemokines. Trends Cardiovasc Med 2004; 14: 161-165
• 32 Cagnin S, Biscuola M, Patuzzo C, Trabetti E, Pasquali A, Laveder P, Faggian G, Iafrancesco M, Mazzucco A, Pignatti PF, Lanfranchi G. Reconstruction and functional analysis of altered molecular pathways in human atherosclerotic arteries. BMC Genomics 2009; 10: 13-27
• 33 Xu F, Lv S, Chen Y, Song X, Jin Z, Yuan F, Zhou Y, Li H. Macrophage inflammatory protein-1β and fibrinogen are synergistic predictive markers of prognosis of intermediate coronary artery lesions. Cardiology 2012; 121: 12-19
• 34 Falcone C, Minoretti P, D’Angelo A, Buzzi MP, Coen E, Emanuele E, Aldeghi A, Olivieri V, Geroldi D. Markers of eosinophilic inflammation and risk prediction in patients with coronary artery disease. Eur J Clin Invest 2006; 36: 211-217
• 35 Haley KJ, Lilly CM, Yang JH, Feng Y, Kennedy SP, Turi TG, Thompson JF, Sukhova GH, Libby P, Lee RT. Overexpression of eotaxin and the CCR3 receptor in human atherosclerosis: using genomic technology to identify a potential novel pathway of vascular inflammation. Circulation 2000; 102: 2185-2189
• 36 Emanuele E, Falcone C, D’Angelo A, Minoretti P, Buzzi MP, Bertona M, Geroldi D. Association of plasma eotaxin levels with the presence and extent of angiographic coronary artery disease. Atherosclerosis 2006; 186: 140-145
• 37 Bennett JMH, Mehta S, Rhodes M. Surgery for morbid obesity. Postgraduate Med J 2007; 83: 8-15
• 38 Sirbu A, Copăescu C, Martin S, Barbu C, Olaru R, Fica S. Six months results of laparoscopic sleeve gastrectomy in treatment of obesity and its metabolic complications. Chirurgia 2012; 107: 469-475
• 39 Dogan M, Tugmen C, Kebapci E, Karaman K, Ozturk S, Olmez M, Karaca C, Bademkiran E, Gorgun M, Aydin C. Effective weight control and normalization of metabolic parameters after laparoscopic sleeve gastrectomy: a single center experience. Hepatogastroenterology 2013; 60: 368-3671
• 40 Gumbau V, Bruna M, Canelles E, Guaita M, Mulas C, Basés C, Celma I, Puche J, Marcaida G, Oviedo M, Vázquez A. A Prospective Study on Inflammatory Parameters in Obese patients after Sleeve Gastrectomy. Obes Surg 2014; 24: 903-908
• 41 Trachta P, Dostálová I, Haluzíková D, Kasalický M, Kaválková P, Drápalová J, Urbanová M, Lacinová Z, Mráz M, Haluzík M. Laparoscopic sleeve gastrectomy ameliorates mRNA expression of inflammation-related genes in subcutaneous adipose tissue but not in peripheral monocytes of obese patients. Mol Cell Endocrinol 2014; 383: 96-102