Download PDF
Horm Metab Res 2016; 48(12): 847-853
DOI: 10.1055/s-0042-108731
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

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

A. Gentili
1   Internal Medicine, Angiology and Atherosclerosis, Department of Medicine, “Santa Maria della Misericordia” Hospital, University of Perugia, Italy
2   Clore Laboratory, Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham, UK
,
M. S. Zaibi
2   Clore Laboratory, Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham, UK
,
S. Y. Alomar
3   Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
,
S. De Vuono
1   Internal Medicine, Angiology and Atherosclerosis, Department of Medicine, “Santa Maria della Misericordia” Hospital, University of Perugia, Italy
,
M. A. Ricci
1   Internal Medicine, Angiology and Atherosclerosis, Department of Medicine, “Santa Maria della Misericordia” Hospital, University of Perugia, Italy
,
A. Alaeddin
1   Internal Medicine, Angiology and Atherosclerosis, Department of Medicine, “Santa Maria della Misericordia” Hospital, University of Perugia, Italy
,
D. Siepi
1   Internal Medicine, Angiology and Atherosclerosis, Department of Medicine, “Santa Maria della Misericordia” Hospital, University of Perugia, Italy
,
M. Boni
4   Department of Surgery, “San Giovanni Battista” Hospital, Foligno, Perugia, Italy
,
G. Vaudo
1   Internal Medicine, Angiology and Atherosclerosis, Department of Medicine, “Santa Maria della Misericordia” Hospital, University of Perugia, Italy
,
P. Trayhurn
2   Clore Laboratory, Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham, UK
3   Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
,
G. Lupattelli
1   Internal Medicine, Angiology and Atherosclerosis, Department of Medicine, “Santa Maria della Misericordia” Hospital, University of Perugia, Italy
› Author Affiliations
Further Information

Publication History

received 03 March 2016

accepted 04 May 2016

Publication Date:
14 June 2016 (online)

Also available at
    Permissions and Reprints

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
    PubMedGoogle Scholar
  • 2 Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011; 29: 415-445
    CrossrefPubMedGoogle Scholar
  • 3 Trayhurn P, Wood IS. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans 2005; 33: 1078-1081
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 7 Panee J. Monocyte chemoattractant protein 1 (MCP-1) in obesity and diabetes. Cytokine 2012; 60: 1-12
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 22 Beltowski J. Leptin and atherosclerosis. Atherosclerosis 2006; 189: 47-60
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 29 Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clin Chim Acta 2007; 380: 24-30
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 31 Boisvert WA. Modulation of atherogenesis by chemokines. Trends Cardiovasc Med 2004; 14: 161-165
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 37 Bennett JMH, Mehta S, Rhodes M. Surgery for morbid obesity. Postgraduate Med J 2007; 83: 8-15
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar