Obesity and Adipokines

Öz

Obesity is defined as an excessive increase in adipose tissue. Studies in recent years, white adipose tissue is revealed as an endocrine organ can produce and release several bioactive polypeptides known as adipokines. In these studies, the adipokines has been shown to play an important role in the development of diseases associated with obesity including insulin resistance, inflammation, hypertension, cardiovascular and metabolic disorders. In this review, obesity-related adipokines, cytokines and their functions are given information about

Anahtar Kelimeler

• Adipose tissue
• Obesity
• Adipokines
• Cytokines

OBEZİTE VE ADİPOKİNLER

Öz

Obesite yağ dokusunun aşırı artışı olarak tanımlanır. Son yıllarda yapılan çalışmalar, beyaz yağ dokusunun, adipokinler olarak tanımlanan bir grup biyoaktif polipeptidi üretip-sekrete edebilen endokrin bir organ olduğunu ortaya çıkarmıştır. Yapılan bu çalışmalarda adipokinlerin insülin direnci, enflamasyon, hipertansiyon, kardiyovasküler ve metabolik bozukluklar gibi obesite ile
ilişkili bir grup hastalığın gelişiminde önemli role sahip olduğu gösterilmiştir. Bu derlemede obezite ile ilgili tanımlanmış adipokinler, sitokinler ve onların fonksiyonları hakkındaki bilgiler verilmiştir.

Anahtar Kelimeler

• Yağ dokusu
• Obezite
• Adipokinler
• Sitokinler

Kaynakça

1. Dina C. New insights into the genetics of body weight. Curr Opin Clin Nutr Metab
2. Care 2008;11:378-384.
3. Reaven G, Abbasi F, McLaughlin T. Obesity, insulin resistance and cardiovascular
4. disease. Recent Prog Horm Res 2004;59:207-223.
5. Shamseddeen H, Getty JZ, Hamdallah IN, Ali MR. Epidemiology and economic
6. impact of obesity and type 2 diabetes. Surg Clin North Am 2001;91:1163-1172
7. Türkiye Beslenme ve Sağlık Araştırması 2010. http://ekutuphane.sagem.gov.tr/kitaplar
8. Jacobi D, Stanya KJ, Lee CH. Adipose tissue signaling by nuclear receptors in

9. metabolic complications of obesity. Adipocyte 2012;1(1):4-12
10. Nadir I, Oğuz D. Adipokinler. Güncel Gastroenteroloji Dergisi. 2009; 13; 107-109.
11. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional
12. cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432.
13. Mehta S, Farmer JA. Obesity and inflamation: A new look at an old problem. Curr
14. Atheroscler Rep 2007;9:134-138.
15. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of
16. adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and
17. subcutaneous adipose tissues of obese humans. Endocrinology 2004;14:52273-52282.
18. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB
19. protein: evidence for a peripheral signal linking adiposity and central neural networks.
20. Science 1995;269:546-549.
21. Chen G, Koyama K, Yuan X, Lee Y, Zhou YT, O'Doherty R, Newgard CB, Unger
22. RH. Disappearance of body fat in normal rats induced by adenovirus-mediated leptin
23. gene therapy. Proc Natl Acad Sci USA. 1996 10;93(25):14795-14799.
24. Orci L, Cook WS, Ravazzola M, Wang MY, Park BH, Montesano R, Unger RH.
25. Rapid transformation of white adipocytes into fat-oxidizing machines. Proc Natl Acad
26. Sci USA. 2004 17;101(7):2058-2063.
27. Vazquez-Vela MEF, Torres N, Tovar AR. White adipose tissue as endocrine organ
28. and its role in obesity. Arch Med Res 2008;39:715-728.
29. Coppari R, Bjorbaek C. Leptin revisited: its mechanisms of action and potential for
30. treating diabetes. Nat Rev Drug Discov 2012;11:692-708
31. Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley
32. GB, Bao C, Noble PW, Lane MD, Diehl AM. Leptin regulates proinflammatory
33. immune responses. FASEB J 1998;12:57-65.
34. Konstantidines S, Schafer K, Koschnick S, Loskutoff DJ. Leptin-dependent platelet
35. aggregation and arterial thrombosis suggests a mechanism of atherothrombotic disease
36. in obesity. J Clin Invest 2001;108:1533-1540.
37. Scherer PE, Williams S, Flogiano M, Baldini G, Lodish HF. A novel serum protein
38. similar to C1q, produced exclusively by adipocytes. J Biol Chem 1995;270:26746–
39. -
40. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, et al.
41. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating
42. AMP-activated protein kinase. Nat Med 2002;8:1288-1295.
43. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev
44. ;26:439-451.
45. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Adipocytederived
46. plasma protein, adiponectin, suppresses lipid accumulation in class A
47. scavenger receptors expression in human monocyte-derived macrophages. Circulation
48. ;103:1057-1063.
49. Fernandez-Real JM, Lopez-Bermejo A, Casamitjana R, Ricart W. Novel interactions
50. of adiponectin with the endocrine system and inflammatory parameters. J Clin
51. Endocrinol Metab 2003;88:2714-2718.
52. Turer AT, Khera A, Ayers CR, Turer CB, Grundy SM, Vega GL, Scherer PE. Adipose
53. tissue mass and location affect circulating adiponectin levels. Diabetologia
54. ;54:2515-2524.
55. Juan-Vague I, Alessi MC, Vague P. Increased plasma plasminogen activator inhibitor
56. levels. A possible link between insulin resistance and atherothrombosis.
57. Diabetologia 1991;34:457-462.
58. Appel SJ, Harrell JS, Davenport ML. Central obesity, the metabolic syndrome and
59. plasminogen activator inhibitor-1 in young adults. J Am Acad Nurse Pract
60. ;17:535-541.
61. Siklova-Vitkova M, Klimcakova E, Polak J, Kovacova Z, Tencerova M, Rossmeislova
62. L, et al. Adipose tissue secretion and expression of adipocyte-produced and
63. stromavascular fraction-produced adipokine vary during multiple phases of weightreducing
64. dietary intervention in obese women. J Clin Endocrinol Metab
65. ;97:1176-1181.
66. Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL,
67. McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB. Prevention of obesity and
68. insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes.
69. ;53(2):336-346.
70. Gurlek A, Bayraktar M, Kirazli S: Increased plasminogen activator inhibitor-1 activity
71. in offspring of type 2 diabetic patients: lack of association with plasma insulin levels.
72. Diabetes Care. 2000;23(1):88-92.
73. Festa A, D’Agostino R Jr, Tracy RP, Haffner SM: Elevated levels of acute-phase
74. proteins and plasminogen activator inhibitor-1 predict the development of type 2
75. diabetes: the Insulin Resistance Atherosclerosis Study. Diabetes 2002;51:1131-1137.
76. Massiera F, Bloch-Faure M, Ceiler D, Murakami K, Fukamizu A, Gasc JM, Quignard-
77. Boulange A, Negrel R, Ailhaud G, Seydoux J, Meneton P, Teboul M. Adipose
78. angiotensinogen is involved in adipose tissue growth and blood pressure regulation.
79. FASEB J 2001;15:2727-2729.
80. Bloem LJ, Manatunga AK, Tewksbury DA, Pratt JH. The serum angiotensinogen
81. concentration and variants of the angiotensinogen gene in white and black children. J
82. Clin Invest. 1995;95(3):948-953.
83. Forrester T, McFarlane-Anderson N, Bennet F, Wilks R, Puras A, Cooper R, Rotimi
84. C, Durazo R, Tewksbury D, Morrison L. Angiotensinogen and blood pressure among
85. blacks: findings from a community survey in Jamaica. J Hypertens. 1996;14(3):315-
86. 32. Yiannikouris F, Karounos M, Charnigo R, English VL, Rateri DL, Daugherty A, and
87. Cassis LA. Adipocyte-specific deficiency of angiotensinogen decreases plasma
88. angiotensinogen concentration and systolic blood pressure inmice. Am J Physiol
89. Regul Integr Comp Physiol 2012;302:R244-R251.
90. Lin Y, Rajala MW, Berger JP, Moller DE, Barzilai N, Scherer PE. Hyperglycemia
91. induced production of acute phase reactants in adipose tissue. J Biol Chem
92. ;276:42077-42083.
93. Poitou C, Viguerie N, Cancello R, De Matteis R, Cinti S, Stich V, Coussieu
94. C, Gauthier E, Courtine M, Zucker JD, et al. Serum amyloid A: production by human
95. white adipocytes and regulation by obesity and nutrition. Diabetologia 2005;48:519-
96. -
97. Johnson BD, Kip KE, Marroquin OC, Ridker PM, Kelsey SF, Shaw LJ, Pepine CJ, et
98. al. Serum amyloid A as a predictor of coronary heart disease and cardiovascular
99. outcome in women: the National Heart, Lung, and Blood Institute Sponsored
100. Women's Ischemia Syndrome Evaluation (WISE). Circulation 2004;109:726-732.
101. Ogasawara K, Mashiba S, Wada Y, et al. A serum amyloid A and LDL complex as a
102. new prognostic marker in stable coronary artery disease. Atherosclerosis
103. ;174:349–56.
104. King VL, Thompson J, Tannock LR. Serum amyloid A in atherosclerosis. Curr Opin
105. Lipidol 2011;22:302-307.
106. Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes.
107. Nature 2001;409:307-312.
108. Verma S, Li SH,Wang CH, et al. Resistin promotes endothelial cell activation: further
109. evidence of adipokine–endothelial interaction. Circulation 2003;108:736-740.
110. Kusminski CM, Meternan PG, Kumar S. Role of resistin in obesity, insülin resistance
111. and Type II diabetes. Clinical Science 2005;109:243-256.
112. Hirai K, Hussey HJ, Barber MD, Price SA, Tisdale MJ. Biological evaluation of a
113. lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Res
114. ;58:2359-2365.
115. Sanders PM, Tisdale MJ. Effect of zinc-α2-glycoprotein (ZAG) on expression of
116. uncoupling proteins in skeletal muscle and adipose tissue. Cancer Lett 2004;212:71-
117. -
118. Gong FY, Zhang SJ, Deng JY, et al. Zinc-alpha2-glycoprotein is involved in
119. regulation of body weight through inhibition of lipogenic enzymes in adipose tissue.
120. Int J Obes 2009;33:1023-1030.
121. Yeung DCY, Lam KSL, Wang Y, Tso AW, Xu A. Serum zinc-α2-glycoprotein
122. correlates with adiposity, triglycerides, and the key components of the metabolic
123. syndrome in Chinese subjects. J Clin Endocrinol Metab 2009;94:2531-2536.
124. Ashley EA, Powers J, Chen M, et al. The endogenous peptide apelin potently
125. improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc Res
126. ;65:73-82.
127. Wei L, Hou X, Tatemoto K. Regulation of apelin mRNA expression by insülin and
128. glucocorticoids in mouse 3T3-L1 adipocytes. Regul Pept 2005;132:27-32.
129. Yu S, Zhang Y, Li MZ, et al. Chemerin and apelin are positively correlated with
130. inflammation in obese type 2 diabetes patients. Chin Med J 2012;125:3440-3444.
131. Kloting N, Graham TE, Berndt J, et al. Serum retinol-binding protein is more highly
132. expressed in visceral than in subcutaneous adipose tissue and is a marker of intraabdominal
133. obesity fat mass. Cell Metab 2007;6:79-87.
134. Graham TE, Yang Q, Bluher M, et al. Retinol binding protein 4 contributes to insülin
135. resistance in lean, obese, and diabetic subjects. N Engl J Med 2006;354:2552-2563.
136. Hammarstedt A, Graham TE, Kahn BB. Adipose tissue dysregulation and reduced
137. insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells.
138. Diabetol Metab Syndr 2012 19;4(1):42. doi: 10.1186/1758-5996-4-42.
139. Hida K, Wada J, Eguchi J, et al. Visceral adipose tissue-derived serine protease
140. inhibitor: a unique insulin-sensititizing adipocytokine in obesity. Proc Natl Acad Sci
141. USA 2005;102:10610-10615.
142. Chang HM, Lee HJ, Park HS, et al. Effects of weight reduction on serum vaspin
143. concentrations in obese subjects: modifications by insulin resistance. Obesity
144. ;18:2105-2110.
145. Kloting N, Kovacs P, Kern M, et al. Central vaspin administration acutely reduces
146. food intake and has sustained blood glucose-lowering effects. Diabetologia
147. ;54:1819-1823.
148. Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin: a protein secreted by visceral
149. fat that mimics the effects of insulin. Science 2005;307:426-430.
150. Chang YH, Chang DM, Lin KC, Shin SJ, Lee YJ. Visfatin in overweight/obesity type
151. diabetes mellitus insulin resistance, metabolic syndrome and cardiovascular
152. diseases: a meta-analysis and systematic review. Diabetes Metab Res Rev
153. ;27:515-527.
154. Kim SR, Bae YH, Bae SK, et al. Visfatin enhances ICAM-1 and VCAM-1 expression
155. through ROS-dependent NF-kappaB activation in endothelial cells. Biochim Biophys
156. Acta 2008;1783:886-895.
157. Yang RZ, Lee MJ, Hu H, et al. Identification of omentin as a novel depot-specific
158. adipokine in human adipose tissue: possible role in modulating insulin action. Am J
159. Physiol Endocrinol Metab 2006;290:E1253-1261.
160. Zhong X, Li X, Liu F, Tan H, Shang D. Omentin inhibits TNF-α-induced expression
161. of adhesion molecules in endothelial cells via ERK/NF-kB pathway. Biochem
162. Biophys Res Commun 2012;425:406-410.
163. Zhong X, Zhang HY, Tan H, et al. Association of serum omentin-1 levels with
164. coronary artery disease. Acta Pharmacol Sin 2011;32:873878.
165. Wittamer V, Franssen JD, Vulcano M, et al. Specific recruitment of antigenpresenting
166. cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp
167. Med 2003;198:977-985.
168. Goralski KB,McCarthy TC, Hanniman EA, et al. Chemerin, a novel adipokine that
169. regulates adipogenesis and adipocyte metabolism. J Biol Chem 2007;282:28175-
170. 62. Takahashi M, Takahashi Y, Takahashi FN, et al. Chemerin enhances insulin signaling
171. and potentiates insulin-stimulated glucose uptake in 3T3-L1adypocytes. FEBS Lett
172. ;582:573-578.
173. Sell H, Laurencikiene J, Taube A, et al. Chemerin is a novel adipocyte-derived factor
174. inducing insulin resistance in primary human skeletal muscle cells. Diabetes
175. ;58:2731-2740.
176. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a
177. growth hormone-releasing acylated peptide from stomach. Nature. 1999 Dec 9; 402
178. (6762): 656-60.
179. Aydoğan A, Akküçük S, Özkan OV, Aydın M, Motor S, Uğur M, Oruç C, Yönden Z.
180. The Protective Effects Of Peptide YY And Ghrelin In Acute Biliary Pancreatitis. Acta
181. Medica Mediterranea, 2014, 30(2): 323-327
182. Der Lely A.J, Ghigo E. Non-acylated ghrelin counteracts the metabolic but not the
183. neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab
184. ;89: 3062-3065.
185. Tombran-Tink J, Chader GG, Johnson LV. PEDF: a pigment epithelium-derived
186. factor with potent neuronal differentiative activity. Experimental eye research.
187. ;53(3):411-4.
188. Yüksel R. Homozigot Hbss Erişkin Orak Hücre Anemili Hastalarda Serum PEDF
189. Düzeyleri ile hsCRP Arasındaki ilişkinin incelenmesi. Uzmanlık Tezi, Hatay: Mustafa
190. Kemal Üniversitesi Tayfur Ata Sökmen Tıp Fakültesi, Tıbbi Biyokimya AD, 2014
191. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW.
192. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest
193. ;112:1796-1808.
194. Lumeng C, Bodzin J, Saltiel A. Obesity induces phenotypic switch in adipose tissue
195. macrophage polarization. J Clin Invest 2007;117:175-184.
196. Lorenzo M, Fernandez-Veledo S, Vila-Bedmar R, et al. Insulin resistance induced by
197. tumor necrosis factor-alpha in myocytes and brown adipocytes. J Anim Sci
198. ;86:E94-104.
199. Romanatto T, Roman EA, Arruda AP, et al. Deletion of the tumor necrosis factor-α
200. receptor 1 (TNFR1) protects against diet-induced obesity by means of increased
201. thermogenesis. J Biol Chem 2009;284:36213-36222.
202. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis
203. factor-alpha: direct role in obesity linked-insulin resistance. Science 1993;259:87-91.
204. Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissuederived
205. cytokines: in vivo and in vitro investigations in humans. Am J Physiol
206. Endocrinol Metab 2003;285:E257-533.