Some metabolic effects of chemerin and relationship with obesity

Öz

Chemerin is a protein found in the liver, lung, placenta, and many tissues, mainly white adipose tissue. Chemerin acts by binding to ChemR23 or CMKLR1 receptors. Chemokine receptorlike 2 is the receptor of the third chemerin receptor discovered in recent years. Chemerin mainly causes inflammation in adipose tissue by binding to the ChemR23 receptor. In addition, it causes rheumatoid arthritis in the joints, non-alcoholic fatty liver disease in the liver, melanoma of the skin and deterioration of healthy skin functions, allergic asthma in the respiratory tract, polycystic ovary syndrome in women, and preterm birth. Since chemerin identified as an adipokine involved in the chemotaxis of leukocytes in adipose tissue in obese individuals, it is recognized as a link between obesity and inflammation, but this role has not been fully specified. The autocrine response of the chemerin in adipose tissue is to activate the metabolic pathways of lipolysis, glucose uptake, and lipostatic signaling. The paracrine response activates the release of inflammatory agents involved in the pathogenesis of obesity. Suppressing these effects of chemerin on adipose tissue can be considered as a new approach in the prevention of obesity, which is an endocrine disease. In this study, the metabolic effects of chemerin on obesity were tried to be revealed.

Anahtar Kelimeler

• chemerin
• inflammation
• adipose tissue
• obesity
• kemerin
• inflamasyon
• adipoz doku
• obezite

Kemerinin bazı metabolik etkileri ve obezite ile ilişkisi

Öz

Kemerin başta beyaz adipoz doku olmak üzere karaciğer, akciğer, plasenta ve birçok dokuda bulunan bir proteindir. Kemerin ChemR23 veya CMKLR1 reseptörlerine bağlanarak etki göstermektedir. Kemokin reseptör benzeri 2 son yıllarda keşfedilen üçüncü kemerin reseptörüdür. Kemerin, özellikle ChemR23 reseptörüne bağlanarak temel olarak adipoz dokuda inflamasyona neden olmaktadır. Ek olarak eklemlerde romatoid artrite, karaciğerde non-alkolik yağlı karaciğer hastalığına, deride melonoma ve sağlıklı deri fonksiyonlarının bozulmasına, solunum yollarında alerjik astıma, kadınlarda polikistik over sendromuna ve erken doğumlara neden olmaktadır. Kemerin obez bireylerde adipoz dokuda bulunan lökositlerin kemotaksisinde görevli bir adipokin olarak tanımlandığı için, obezite ve inflamasyon arasında bir bağlantı olarak kabul edilmiş, ancak bu rolü tam olarak belirtilmemiştir. Adipoz dokuda kemerinin otokrin cevabı lipoliz, glikoz alımı ve lipostatik sinyalleme metabolik yollarını aktive etmektir. Parakrin cevabı ise obezitenin patogenezinde yer alan inflamatuvar ajanların salınımını aktive etmektir. Kemerinin adipoz dokudaki bu etkilerinin baskılanması, endokrin bir hastalık olan obezitenin önlenmesinde yeni bir yaklaşım olarak düşünülebilir. Bu çalışmada, kemerinin obezite üzerine metabolik etkileri ortaya konmaya çalışılmıştır.

Anahtar Kelimeler

• kemerin
• inflamasyon
• adipoz doku
• obezite

Kaynakça

1. 1.NCD Risk Factor Collaboration (NCDRisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet. 2016;387(10026):1377-96.
2. 2.NCD Risk Factor Collaboration (NCDRisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627-42.
3. 3.Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288-98.
4. 4. Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010;363(23):2211-9.
5. 5. World Health Organization. 2016. Erişim: www.who.int/mediacentre/factsheets/fs311/en/. Erişim tarihi: March 19, 2020.
6. 6. Bray GA, Kim KK, Wilding JPH, World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 2017;18(7):715-23.
7. 7. Reddy NL, Tan BK, Barber TM, et al. Brown adipose tissue: endocrine determinants of function and therapeutic manipulation as a novel treatment strategy for obesity. BMC Obes. 2014;1:13.
8. 8. Payab M, Abedi M, Heravani NF, et al. Brown adipose tissue transplantation as a novel alternative to obesity treatment: a systematic review. Int J Obes. 2020;1-13.

9. 9. Gentili A, Zaibi MS, Alomar SY, et al. Circulating levels of the adipokines monocyte chemotactic protein‐4 (mcp‐4), macrophage inflammatory protein‐1β (mıp‐1β), and eotaxin‐3 in severe obesity and following bariatric surgery. Horm Metab Res. 2016;48(12):847-53.
10. 10. Ministrini S, Ricci MA, Nulli Migliola E, et al. Chemerin predicts carotid intima‐media thickening in severe obesity. Eur J Clin Invest. 2020;50(8):e13256.
11. 11. Ernst MC, Sinal CJ. Chemerin: at the crossroads of inflammation and obesity. Trends Endocrinol Metab. 2010;21:660-7.
12. 12. Bondue B, Wittamer V, Parmentier M. Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Cytokine Growth Factor Rew. 2011;22:331-8.
13. 13.Takahashi M, Okimura Y, Iguchi G, et al. Chemerin regulates beta-cell function in mice. Sci Rep. 2011;1:123.
14. 14.Issa ME, Muruganandan S, Ernst MC, et al. Chemokine-like receptor 1 regulates skeletal muscle cell myogenesis. Am. J. Physiol-Cell Physiol. 2012;302(11):1621-31.
15. 15.Zabel BA, Ohyama T, Zuniga L, et al. Chemokine like receptor 1 expression by macrophages in vivo: regulation by TGF-beta and TLR ligands. Exp Hematol. 2006;34:1106-14.
16. 16. Nagpal S, Patel S, Jacobe H, et al. Tazaroteneinduced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Investig Dermatol. 1997;109:91-5.
17. 17. Wittamer V, Franssen JD, Vulcano M, et al. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med. 2003;198:977-85.
18. 18.Allen SJ, Zabel BA, Kirkpatrick J, et al. NMR assignment of human chemerin, a novel chemoattractant. Biomol NMR Assign. 2007;1:171-3.
19. 19.Zabel BA, Silverio AM, Butcher EC. Chemokine-like receptor 1 expression and chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood. J Immunol. 2005;174:244-51.
20. 20. Fatıma SS, Rehman R, Baig M, et al. New roles of the multidimensional adipokine: chemerin. Peptides. 2014;62:15-20.
21. 21. Jialal I, Devaraj S, Kaur H, et al. Increased chemerin and decreased omentin-1 in both adipose tissue and plasma in nascent metabolicsyndrome. J Clin Endocrinol Metab. 2013;98(3):514-7.
22. 22.Shin HY, Lee DC, Chu SH, et al. Chemerin levels are positively correlated with abdominal visceral fat accumulation. Clin Endocrinol(Oxf). 2012;77(1):47-50.
23. 23.Martinez-Garcia MA, Montes-Nieto R, Fernandez-Duran E, et al. Evidence for masculinization of adipokine gene expression in visceral and subcutaneous adipose tissue of obese women with polycystic ovary syndrome (PCOS). J Clin Endocrinol Metab. 2013;98:388-96.
24. 24.Goralski KB, Mccarthy TC, Hanniman EA, et al. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem. 2007;282:175-88.
25. 25.Roh SG, Song SH, Choi KC, et al. Chemerin : a new adipokine that modulates adipogenesis via its own receptor. Biochem Biophys Res Commun. 2007;362:1013-8.
26. 26.Parlee SD, Ernst MC, Muruganandan S, et al. Serum chemerin levels vary with time of day and are modified by obesity and tumor necrosis factor-alfa. End. 2010;151(6):2590-2602.
27. 27. Kralisch S, Weise S, Sommer G, et al. Interleukin 1ss induces the novel adipokine chemerin in adipocytes in vitro. Regul Pept. 2009;154:102-6.
28. 28. Bauer S, Wanninger J, Schmidhofer S, et al. Sterol regulatory element-binding protein 2 (SREBP2) activation after excess triglyceride storage induces chemerin in hypertrophic adipocytes. Endocrinology. 2011;152:26-35.
29. 29.Samson M, Edinger AL, Stordeur P, et al. ChemR23, a putative chemoattractant receptor, is expressed in monocytederived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV1 strains. Eur J Immunol. 1998;28:1689-1700.
30. 30.Parolini S, Santoro A, Marcenaro E, et al. The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues. Blood. 2007;109:3625-32.
31. 31. Vermi W, Riboldi E, Wittamer V, et al. Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin. J Exp Med. 2005;201:509-15.
32. 32. Sell H, Laurencikiene J, Taube A, et al. Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells. Diabetes. 2009;58:2731-40.
33. 33. Kaur J, Adya R, Tan BK, et al. Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis. Biochem Biophys Res Commun. 2010; 391:1762-68.
34. 34. Herova M., Schmid M, Gemperle C, et al. ChemR23, the receptor for chemerin and resolvin E1, is expressed and functional on M1 but not on M2 macrophages. The Journal of Immunology. 2015; 194(5):2330-7.
35. 35. Arita M, Bianchini F, Aliberti J, et al. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med. 2005;201:713-22.
36. 36. Barnea G, Strapps W, Herrada G, Berman Y, Ong J, Kloss B. The genetic design of signaling cascades to record receptor activation. Proc Natl Acad Sci USA. 2008;105(1): 64-69.
37. 37. Zabel BA, Nakae S, Zuniga L, et al. Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis. J Exp Med. 2008;205:2207-20.
38. 38.Migeotte I, Franssen JD, Goriely S, et al. Distribution and regulation of expression of the putative human chemokine receptor HCR in leukocyte populations. Eur J Immunol. 2002;32:494-501.
39. 39.Biber K, Zuurman MW, Homan H, et al. Expression of L-CCR in HEK 293 cells reveals functional responses to CCL2, CCL5, CCL7, and CCL8. J Leukoc Biol. 2003;74:243-51.
40. 40.Mariani F, Roncucci L. Chemerin/chemR23 axis in inflammation onset and resolution. Inflammation Research. 2015;64(2):85-95.
41. 41. Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol. 2014;220:47-59.
42. 42. Muruganandan S, Roman AA, Sinal CJ. Role of chemerin/CMKLR1 signaling in adipogenesis and osteoblastogenesis of bone marrow stem cells. J Bone Miner Res. 2010;25(2):222-34.
43. 43. Cash JL, Hart R, Russ A, et al. Synthetic chemerin derived peptides suppress inflammation through CHEM R23. J Exp Med. 2008;205:767-75.
44. 44. Karlsson C, Lindell K, Ottosson M, et al. Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II. The Journal of Clinical Endocrinology and Metabolism. 1998;83(11):3925-9.
45. 45.Lopez X, Castells M, Ricker A, et al. Human insulin analog–induced lipoatrophy. Diabetes Care. 2008;31(3):442-4.
46. 46.Chan S-S, Eisenberg D, Zhao L, et al. Chemerin activation in human obesity. Obesity. 2016;24(7):1522-9.
47. 47. Bozaoglu K, Curran JE, Stocker CJ, et al. Chemerin, a Novel Adipokine in the Regulation of Angiogenesis. JCEM. 2010;95(5):2476-85.
48. 48. Tan BK, Chen J, Farhatullah S, et al. Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes. 2009;58(9):1971-7.
49. 49. Helfer G, Ross AW, Thomson LM, et al. A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance. Scientific Reports. 2016;6:26830.
50. 50. Chu SH, Lee MK, Ahn KY, et al. Chemerin and adiponectin contribute reciprocally to metabolic syndrome. PLoS ONE. 2012;7(4):e34710.