A CURRENT ADIPOKINE: CHEMERIN

Year 2019, Volume: 20 Issue: 2, 98 - 104, 29.04.2019

Menşure Nur Çelik , Mehtap Ünlü Söğüt

https://doi.org/10.18229/kocatepetip.557987

Abstract

OBJECTIVE: Chemerin secreted from adipose tissue is a signal molecule with a variety of autocrine and paracrine effects and a new chemotactic protein that recently joined the adipokine family. In recent years, chemerin and its receptor are expressed at the highest levels in adipocytes and less expressed than in the liver, kidney, pancreas, pituitary, placenta, ovary and testes. Through these organs and tissues it is known that it affects energy homeostasis, glucose metabolism, inflammation and many physiological processes. There is growing evidence that this adipokine has been shown to play a role in adipogenesis, energy metabolism and inflammation, its role in metabolic syndrome (MetS), obesity, Type 2 Diabetes Mellitus (T2DM), cardiovascular diseases, Crohn’s disease, arthritis and cancer. In particular, chemerin has been suggested as a hypothesis of a possible link between obesity and the development of T2DM. It was also found that plasma chemerin levels correlated positively with body mass index, fasting serum insulin, fasting blood glucose, plasma triglycerides and total serum cholesterol and negatively correlated with high density lipoprotein (HDL). In general, these findings indicate that circulating levels of chemerin are dependent on adiposity and metabolic syndrome, suggesting that visceral adipose is a replaceable source of chemerin in obese individuals. Chemerin affects glucose homeostasis by decreasing insulin levels and increasing glucose uptake; T2DM by inhibiting glycogen synthase; inflammation by regulating adipocyte differentiation and chemotaxis; MetS markers by regulating the release of GLUT-4, fatty acid synthase, adiponectin and leptin. Therefore, it is important to determine the levels of circulating levels of chemerin adipokinin in relation to obesity, T2DM, cardiovascular diseases, inflammation, metabolic syndrome and many other diseases. In the literature, it is frequently observed that circulating chemerin levels are high in individuals with obese and metabolic syndrome. In this review, chemerinin is associated with the effects of obesity and the metabolic syndrome, as well as less-studied inflammation, polycystic ovarian syndrome and other metabolic effects.

Keywords

Chemerin, obesity, metabolic syndrome, inflammation

GÜNCEL BİR ADİPOKİN: CHEMERİN

Abstract

AMAÇ: Adipoz dokudan salgılanan chemerin kısa bir süre önce adipokin ailesine katılan, çeşitli otokrin ve parakrin etkileri olan bir sinyal molekülü ve yeni bir kemotaktik proteindir. Son yıllarda chemerin ve reseptörünün adipositlerde yüksek oranda olmak üzere karaciğer, böbrek, pankreas, hipofiz, plasenta, yumurtalık ve testislerde eksprese edildiği saptanmıştır. Bu organ ve dokular aracılığıyla enerji homeostazı, glukoz metabolizması, inflamasyon ve birçok fizyolojik sürece etki ettiği bilinmektedir. Adipogenezis, enerji metabolizması ve inflamasyonda rolü olduğu gösterilen bu adipokinin metabolik sendrom (MetS), obezite, Tip 2 Diabetes Mellitus (T2DM), kardiyovasküler hastalıklar, Crohn hastalığı, artrit ve kanserde rolü hakkında artan kanıtlar mevcuttur. Özellikle chemerin, obezite ile T2DM’ nin gelişimi arasında olası bir bağlantının hipotezi olarak öne sürülmüştür. Aynı zamanda plazma chemerin düzeylerinin vücut kütle indeksi, açlık serum insülini, açlık kan glukozu, plazma trigliseridleri ve total serum kolesterolü ile pozitif korelasyon gösterdiği ve yüksek yoğunluklu lipoprotein (HDL) ile negatif korelasyon gösterdiği saptanmıştır. Genel olarak, bu bulgular dolaşımdaki chemerin düzeylerinin yağlanmaya ve metabolik sendroma bağlı olduğunu, viseral adipozun obez bireylerde chemerinin değiştirilebilir bir kaynağı olduğunu düşündürmektedir. Chemerin; insulin seviyesini azaltıp, glukoz kullanımını artırarak glukoz homeostazını; glikojen sentetazı inhibe ederek T2DM’u; adiposit farklılaşmasını ve kemotaksisi düzenleyerek inflamasyonu; GLUT-4, yağ asidi sentaz, adiponektin ve leptinin salınımını düzenleyerek MetS belirteçlerini etkilemektedir. Bu nedenle obezite, T2DM, kardiyovasküler hastalıklar, inflamasyon, metabolik sendrom ve daha birçok hastalıkla ilişkisi bulunan chemerin adipokininin dolaşımdaki seviyelerini belirlemek ve düzeylerini kontrol etmek önem taşımaktadır. Literatür taramasında sıklıkla obez ve metabolik sendromlu bireylerde dolaşımdaki chemerin seviyelerinin yüksek olduğu göze çarpmaktadır. Bu derlemede chemerinin obezite ve metabolik sendromdaki etkileri ile birlikte daha az ele alınan inflamasyon, polikistik over sendromu ve diğer metabolik etkilerine yer verilmektedir.

Keywords

Chemerin, obezite, metabolik sendrom, inflamasyon

References

• 1.Lehr S., Hartwig S., Sell H. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl 2012; 6(1-2):91-101.
• 2.Rourke JL., Dranse HJ, Sinal CJ. Towards anintegrative approach to understanding the role of chemerin in human health and disease. Obes Rev 2013;14(3):245-62.
• 3.Booth A., Magnuson A., Fouts J., et al. Adipose tissue, obesity and adipokines: role in cancer promotion. Horm Mol Biol Clin Investig 2015;21(1):57-74.
• 4.Mattern A., Zellmann T., Beck-Sickinger AG.Processing, signaling, and physiological function of chemerin. IUBMB Life 2014;66(1):19-26. 103
• 5.Roh SG., Song SH., Choi KC. et al. Chemerin--anew adipokine that modulates adipogenesis via its own receptor. Biochem Biophys Res Commun 2007; 362(4):1013-8.
• 6. Dupont J., Pollet-Villard X., Reverchon M., Mellouk N., Levy R. Adipokines in human reproduction. Horm Mol Biol Clin Investig 2015;24(1):11-24.
• 7.De Henau O., Degroot GN., Imbault V. etal. Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2. PLoS One 2016;11(10):e0164179.
• 8. Ernst MC., Sinal CJ. Chemerin: at the crossroads of inflammation and obesity. Trends Endocrinol Metab 2010;21(11):660-7.
• 9.Roman AA, Parlee SD, Sinal CJ. Chemerin: apotential endocrine link between obesity and type 2 diabetes. Endocrine 2012;42(2):243-51.
• 10.Goralski KB., McCarthy TC., Hanniman EA. etal. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 2007;282(38):28175-88.
• 11.Piya MK., McTernan PG., Kumar S. Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin. J Endocrinol 2013;216(1):T1-T15.
• 12.Chang SS., Eisenberg D., Zhao L. et al. Chemerin activation in human obesity. Obesity (Silver Spring) 2016;24(7):1522-9.
• 13.Bozaoglu K., Bolton K., McMillan J. et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007;148(10):4687-94.
• 14. Ress C., Tschoner A., Engl J. et al. Effect of bariatric surgery on circulating chemerin levels. Eur J Clin Invest 2010;40(3):277-80.
• 15.Chakaroun R., Raschpichler M., Kloting N. etal. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism 2012;61(5):706-14.
• 16.Sell H., Divoux A., Poitou C. et al. Chemerincorrelates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. J Clin Endocrinol Metab 2010;95(6):2892-6.
• 17.Fatima SS., Bozaoglu K., Rehman Ret al. Elevated chemerin levels in Pakistani men: an interrelation with metabolic syndrome phenotypes. PLoS One 2013; 8(2):e57113.
• 18. Thomas S., Kratzsch D., Schaab M. et al. Seminal plasma adipokine levels are correlated with functional characteristics of spermatozoa. Fertil Steril 2013;99(5):1256-63.e3.
• 19.Stejskal D., Karpisek M., Hanulovac Z. et al.Chemerın İs an İndependent marker of the metabolİc syndrome İn a caucasİan population. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2008;52(2):217–21.
• 20.Takahashi M., Takahashi Y., Takahashi K. et al.Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes. FEBS Lett 2008;582(5):573-8.
• 21.Bauer S., Bala M., Kopp A. et al. Adipocytechemerin release is induced by insulin without being translated to higher levels in vivo. Eur J Clin Invest 2012;42(11):1213-20.
• 22.Wassink A., Olijhoek J., Visseren F. The metabolic syndrome metabolic changes with vascular Consequences. European Journal of Clinical Investigation 2007;37(1):8-17.
• 23.Li Y., Shi B., Li S. Association between serumchemerin concentrations and clinical indices in obesity or metabolic syndrome: a meta-analysis. PLoS One 2014;9(12):e113915.
• 24.Erdogan S., Yilmaz FM., Yazici O. et al. Inflammation and chemerin in colorectal cancer. Tumour Biol 2016;37(5):6337-42.
• 25.Wittamer V, Franssen JD, Vulcano M, MirjoletJF, Le Poul E, Migeotte I, et al. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med. 2003;198(7):977-85.
• 26. Fatima SS., Butt Z., Bader N. et al. Role of multifunctional Chemerin in obesity and preclinical diabetes. Obes Res Clin Pract 2015;9(5):507-12.
• 27.Weigert J., Obermeier F., Neumeier M. et al.Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn’s disease. Inflamm Bowel Dis 2010;6(4):630-7.
• 28.Shen W., Tian C., Chen H. et al. Oxidativestress mediates chemerin-induced autophagy in endothelial cells. Free Radic Biol Med 2013;55:73-82.
• 29.Jin CH., Yi KW., Ha YR. et al. Chemerin Expression in the Peritoneal Fluid, Serum, and Ovarian Endometrioma of Women with Endometriosis. Am J Reprod Immunol 2015;74(4):379-86.
• 30.Luangsay S., Wittamer V., Bondue B. et al.Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model. J Immunol 2009;183(10):6489-99.
• 31.Lehrke M., Becker A., Greif M. et al. Chemerinis associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis. Eur J Endocrinol 2009;161(2):339-44.
• 32.Guvenc Y., Var A., Goker A. et al. Assessmentof serum chemerin, vaspin and omentin-1 levels in patients with polycystic ovary syndrome. J Int Med Res 2016;44(4):796-805.
• 33.Kort DH., Kostolias A., Sullivan C. et al. Chemerin as a marker of body fat and insulin resistance in women with polycystic ovary syndrome. Gynecol Endocrinol 2015;31(2):152-5.
• 34.Tan BK., Chen J., Farhatullah S. et al. Insulinand metformin regulate circulating and adipose tissue chemerin. Diabetes 2009;58(9):1971-7.
• 35.Guzel EC., Celik C., Abali R. et al. Omentinand chemerin and their association with obesity in women with polycystic ovary syndrome. Gynecol Endocrinol 2014;30(6):419-22.
• 36.Guducu N. Serum Chemerin Levels In Polycystic Ovary Syndrome. Turkish Journal of Biochemistry 2015;40(2):157–62.
• 37.Rama D., Esendagli G., Guc D. Expression ofchemokine-like receptor 1 (CMKLR1) on J744A.1 macrophages co-cultured with fibroblast and/or tumor cells: modeling the influence of microenvironment. Cell Immunol 2011;271(1):134-40.
• 38.Wang C., Wu WK., Liu X. et al. Increased serum chemerin level promotes cellular invasiveness in gastric cancer: a clinical and experimental study. Peptides 2014;51:131-8.
• 39.Gu P., Jiang W., Lu B. et al. Chemerin is associated with inflammatory markers and metabolic syndrome phenotypes in hypertension patients. Clin Exp Hypertens 2014;36(5):326-32.
• 40.Bonomini M., Pandolfi A. Chemerin in renaldysfunction and cardiovascular disease. Vascular Pharmacology 2016;77:28-34.
• 41.Pfau D., Bachmann A., Lossner U. et al. Serumlevels of the adipokine chemerin in relation to renal function. Diabetes Care 2010;33(1):171-3.
• 42.Kostopoulos C., Spiroglou S., Varakis J., et al.Chemerin and CMKLR1 expression in human arteries and periadventitial fat. BMC Cardiovascular Disorders 2014;14(1):56.
• 43.Dong B, Ji W, Zhang Y. Elevated SerumChemerin Levels are Associated with the Presence of Coronary Artery Disease in Patients with Metabolic Syndrome. Internal Medicine 2011;50(10):1093-7.
• 44.Zabel BA., Allen SJ., Kulig P. et al. Chemerinactivation by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades. J Biol Chem 2005;280(41):34661-6. 104