Adiponectin: A link between obesity and cancer

Expert Opinion on Investigational Drugs

Volumn 15, Issue 8, 2006, Pages 917-931

  Barb, Diana ^a   Pazaitou Panayiotou, Kalliopi ^b   Mantzoros, Christos S ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b THEAGENIO CANCER HOSPITAL   (Greece)

Author keywords

Acrp30; Adiponectin; AMPK; Cancer risk; Insulin resistance; Obesity

Indexed keywords

ADIPONECTIN; ADIPONECTIN RECEPTOR 1; ADIPONECTIN RECEPTOR 2; ANTINEOPLASTIC AGENT; DOXORUBICIN;

ADIPOCYTE; ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; CANCER; CANCER CELL; CANCER RISK; CARCINOGENESIS; CELL PROLIFERATION; CELL TYPE; DISEASE ASSOCIATION; HORMONE RECEPTOR INTERACTION; HUMAN; NONHUMAN; OBESITY; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; TUMOR CELL;

EID: 33746837628     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.15.8.917     Document Type: Review

References (144)

1. The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators. J. Clin. Epidemiol. (1988) 41:105-114.
2. KOPELMAN PG: Obesity as a medical problem. Nature (2000) 404:635-643.
3. WOLK A, GRIDLEY G, SVENSSON M et al.: A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control (2001) 12:13-21.
4. IARC Handbooks on Cancer Prevention, Weight control and physical activity (Volume 6). WHO, IARC Press, Lyon, France (2002).
5. BERGSTROM A, PISANI P, TENET V, WOLK A, ADAMI HO: Overweight as an avoidable cause of cancer in Europe. Int. J. Cancer (2001) 91:421-430.
6. PAN SY, JOHNSON KC, UGNAT AM, WEN SW, MAO Y: Association of obesity and cancer risk in Canada. Am. J. Epidemiol. (2004) 159:259-268.
7. CALLE EE, RODRIGUEZ C, WALKER-THURMOND K, THUN MJ: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N. Engl. J. Med. (2003) 348:1625-1638.
8. WERNER H, LEROITH D: The role of the insulin-like growth factor system in human cancer. Adv. Cancer Res. (1996) 68:183-223.
9. KHANDWALA HM, McCUTCHEON IE, FLYVBJERG A, FRIEND KE: The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr. Rev. (2000) 21:215-244.
10. KLUGE A, ZIMMERMANN R, MUNKEL B et al.: Insulin-like growth factor I is involved in inflammation linked angiogenic processes after microembolisation in porcine heart. Cardiovasc. Res. (1995) 29:407-415.
11. PALMQVIST R, STATTIN P, RINALDI S et al.: Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Int. J. Cancer (2003) 107:89-93.
12. GIOVANNUCCI E: Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J. Nutr. (2001) 131:3109S-3120S.
13. SCHOEN RE, TANGEN CM, KULLER LH et al.: Increased blood glucose and insulin, body size, and incident colorectal cancer. J. Natl. Cancer Inst. (1999) 91:1147-1154.
14. LAWLOR DA, SMITH GD, EBRAHIM S: Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women's Heart and Health Study. Cancer Causes Control (2004) 15:267-275.
15. KAAKS R: Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control (1996) 7:605-625.
16. KAAKS R, LUKANOVA A, KURZER MS: Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol. Biomarkers Prev. (2002) 11:1531-1543.
17. HAMMARSTEN J, HOGSTEDT B: Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur. J. Cancer (2005) 41:2887-2895.
18. McCARTY MF: Chronic activation of AMP-activated kinase as a strategy for slowing aging. Med. Hypotheses (2004) 63:334-339.
19. MANTZOROS CS, TZONOU A, SIGNORELLO LB, STAMPFER M, TRICHOPOULOS D, ADAMI HO: Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br. J. Cancer (1997) 76:1115-1118.
20. BOHLKE K, CRAMER DW, TRICHOPOULOS D, MANTZOROS CS: Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology (1998) 9:570-573.
21. BRUNING PF, VAN DOORN J, BONFRER JM et al.: Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int. J. Cancer (1995) 62:266-270.
22. HANKINSON SE, WILLETT WC, COLDITZ GA et al.: Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet (1998) 351:1393-1396.
23. KAULSAY KK, NG EH, JI CY, HO GH, AW TC, LEE KO: Serum IGF-binding protein-6 and prostate specific antigen in breast cancer. Eur. J. Endocrinol. (1999) 140:164-168.
24. AYABE T, TSUTSUMI O, SAKAI H et al.: Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer. Endocr. J. (1997) 44:419-424.
25. CHAN JM, STAMPFER MJ, GIOVANNUCCI E et al.: Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science (1998) 279:563-566.
26. MA J, POLLAK MN, GIOVANNUCCI E et al.: Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J. Natl. Cancer Inst. (1999) 91:620-625.
27. RENEHAN AG, JONES J, POTTEN CS, SHALET SM, O'DWYER ST: Elevated serum insulin-like growth factor (IGF)-II and IGF binding protein-2 in patients with colorectal cancer. Br. J. Cancer (2000) 83:1344-1350.
28. MANOUSOS O, SOUGLAKOS J, BOSETTI C et al.: IGF-I and IGF-II in relation to colorectal cancer. Int. J. Cancer (1999) 83:15-17.
29. LEE DY, KIM SJ, LEE YC: Serum insulin-like growth factor (IGF)-I and IGF-binding proteins in lung cancer patients. J. Korean Med. Sci. (1999) 14:401-404.
30. YU H, SPITZ MR, MISTRY J, GU J, HONG WK, WU X: Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis. J. Natl. Cancer Inst. (1999) 91:151-156.
31. ROSE DP: Diet, hormones, and cancer. Ann. Rev. Public Health (1993) 14:1-17.
32. BULUN SE, MAHENDROO MS, SIMPSON ER: Aromatase gene expression in adipose tissue: relationship to breast cancer. J. Steroid Biochem. Mol. Biol. (1994) 49:319-326.
33. BARBIERI RL, MAKRIS A, RANDALL RW, DANIELS G, KISTNER RW, RYAN KJ: Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J. Clin. Endocrinol. Metab. (1986) 62:904-910.
34. BERNSTEIN L, ROSS RK: Endogenous hormones and breast cancer risk. Epidemiol. Rev. (1993) 15:48-65.
35. STEPHENSON GD, ROSE DP: Breast cancer and obesity: an update. Nutr. Cancer (2003) 45:1-16.
36. AHIMA RS, FLIER JS: Adipose tissue as an endocrine organ. Trends Endocrinol. Metab. (2000) 11:327-332.
37. NAKANO Y, TOBE T, CHOI-MIURA NH, MAZDA T, TOMITA M: Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J. Biochem. (Tokyo) (1996) 120:803-812.
38. HU E, LIANG P, SPIEGELMAN BM: AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. (1996) 271:10697-10703.
39. SCHERER PE, WILLIAMS S, FOGLIANO M, BALDINI G, LODISH HF: A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. (1995) 270:26746-26749.
40. MAEDA K, OKUBO K, SHIMOMURA I, FUNAHASHI T, MATSUZAWA Y, MATSUBARA K: cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). Biochem. Biophys. Res. Commun. (1996) 221:286-289.
41. PINEIRO R, IGLESIAS MJ, GALLEGO R et al.: Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS Lett. (2005) 579:5163-5169.
42. CHEN J, TAN B, KARTERIS E et al.: Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia (2006) 49(6):1292-1302.
43. TAKAHASHI M, ARITA Y, YAMAGATA K et al.: Genomic structure and mutations in adipose-specific gene, adiponectin. Int. J. Obes. Relat. Metab. Disord. (2000) 24:861-868.
44. KISSEBAH AH, SONNENBERG GE, MYKLEBUST J et al.: Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc. Natl. Acad. Sci. USA (2000) 97:14478-14483.
45. YOKOTA T, ORITANI K, TAKAHASHI I et al.: Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood (2000) 96:1723-1732.
46. OUCHI N, KIHARA S, ARITA Y et al.: Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation (1999) 100:2473-2476.
47. OUCHI N, KIHARA S, ARITA Y et al.: Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation (2001) 103:1057-1063.
48. WONG GW, WANG J, HUG C, TSAO TS, LODISH HF: A family of Acrp30/ adiponectin structural and functional paralogs. Proc. Natl. Acad. Sci. USA (2004) 101:10302-10307.
49. TSAO TS, MURREY HE, HUG C, LEE DH, LODISH HF: Oligomerization state-dependent activation of NF-κB signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30). J. Biol. Chem. (2002) 277:29359-29362.
50. PEAKE PW, KRIKETOS AD, CAMPBELL LV, SHEN Y, CHARLESWORTH JA: The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals. Eur. J. Endocrinol. (2005) 153:409-417.
51. KADOWAKI T, YAMAUCHI T: Adiponectin and adiponectin receptors. Endocr. Rev. (2005) 26:439-451.
52. FRUEBIS J, TSAO TS, JAVORSCHI S et al.: Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc. Natl. Acad. Sci. USA (2001) 98:2005-2010.
53. WAKI H, YAMAUCHI T, KAMON J et al.: Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology (2005) 146:790-796.
54. GOLDSTEIN BJ, SCALIA R: Adiponectin: a novel adipokine linking adipocytes and vascular function. J. Clin. Endocrinol. Metab. (2004) 89:2563-2568.
55. HUG C, WANG J, AHMAD NS, BOGAN JS, TSAO TS, LODISH HF: T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/ adiponectin. Proc. Natl. Acad. Sci. USA (2004) 101:10308-10313.
56. TSAO TS, TOMAS E, MURREY HE et al.: Role of disulfide bonds in Acrp30/ adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J. Biol. Chem. (2003) 278:50810-50817.
57. TOMAS E, TSAO TS, SAHA AK et al.: Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc. Natl. Acad. Sci. USA (2002) 99:16309-16313.
58. BERG AH, COMBS TP, DU X, BROWNLEE M, SCHERER PE: The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat. Med. (2001) 7:947-953.
59. PAJVANI UB, DU X, COMBS TP et al.: Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. J. Biol. Chem. (2003) 278:9073-9085.
60. YAMAUCHI T, KAMON J, MINOKOSHI Y et al.: Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. (2002) 8:1288-1295.
61. PAJVANI UB, HAWKINS M, COMBS TP et al.: Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J. Biol. Chem. (2004) 279:12152-12162.
62. FISHER FF, TRUJILLO ME, HANIF W et al.: Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia (2005) 48:1084-1087.
63. YAMAUCHI T, KAMON J, ITO Y et al.: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature (2003) 423:762-769.
64. KHARROUBI I, RASSCHAERT J, EIZIRIK DL, CNOP M: Expression of adiponectin receptors in pancreatic β cells. Biochem. Biophys. Res. Commun. (2003) 312:1118-1122.
65. 2-terminal kinase and inhibits signal transducer and activator of transcription 3. Biochem. Biophys. Res. Commun. (2005) 333:79-87.
66. TSUCHIDA A, YAMAUCHI T, ITO Y et al.: Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity J. Biol. Chem. (2004) 279:30817-30822.
67. INUKAI K, NAKASHIMA Y, WATANABE M et al.: Regulation of adiponectin receptor gene expression in diabetic mice. Am. J. Physiol. Endocrinol. Metab. (2005) 288:E876-E882.
68. OANA F, TAKEDA H, HAYAKAWA K et al.: Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. Metabolism (2005) 54:995-1001.
69. TSUCHIDA A, YAMAUCHI T, TAKEKAWA S et al.: Peroxisome proliferator-activated receptor (PPAR)α activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARα, PPARγ, and their combination. Diabetes (2005) 54:3358-3370.
70. KALTENBACH S, STAIGER H, WEISSER M et al.: Adiponectin receptor gene expression in human skeletal muscle cells is not regulated by fibrates and thiazolidinediones. Int. J. Obes. (Lond.) (2005) 29:760-765.
71. ADACHI Y, TAKEUCHI T, SONOBE H, OHTSUKI Y: An adiponectin receptor, T-cadherin, was selectively expressed in intratumoral capillary endothelial cells in hepatocellular carcinoma: possible cross talk between T-cadherin and FGF-2 pathways. Virchows Arch. (2006) 448(3):311-318.
72. CNOP M, HAVEL PJ, UTZSCHNEIDER KM et al.: Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia (2003) 46:459-469.
73. NISHIZAWA H, SHIMOMURA I, KISHIDA K et al.: Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes (2002) 51:2734-2741.
74. PAGE ST, HERBST KL, AMORY JK et al.: Testosterone administration suppresses adiponectin levels in men. J. Androl. (2005) 26:85-92.
75. XU A, CHAN KW, HOO RL et al.: Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J. Biol. Chem. (2005) 280:18073-18080.
76. WAKI H, YAMAUCHI T, KAMON J et al.: Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J. Biol. Chem. (2003) 278:40352-40363.
77. COMBS TP, BERG AH, RAJALA MW et al.: Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes (2003) 52:268-276.
78. HOFFSTEDT J, ARVIDSSON E, SJOLIN E, WAHLEN K, ARNER P: Adipose tissue adiponectin production and adiponectin serum concentration in human obesity and insulin resistance. J. Clin. Endocrinol. Metab. (2004) 89:1391-1396.
79. GALE SM, CASTRACANE VD, MANTZOROS CS: Energy homeostasis, obesity and eating disorders: recent advances in endocrinology. J. Nutr. (2004) 134:295-298.
80. GARG A: Acquired and inherited lipodystrophies. N. Engl. J. Med. (2004) 350:1220-1234.
81. GAVRILA A, CHAN JL, YIANNAKOURIS N et al.: Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J. Clin. Endocrinol. Metab. (2003) 88:4823-4831.
82. ARITA Y, KIHARA S, OUCHI N et al.: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. (1999) 257:79-83.
83. QI L, RIMM E, LIU S, RIFAI N, HU FB: Dietary glycemic index, glycemic load, cereal fiber, and plasma adiponectin concentration in diabetic men. Diabetes Care (2005) 28:1022-1028.
84. HOTTA K, FUNAHASHI T, ARITA Y et al.: Plasma concentrations of a novel, adipose-specific protein, adiponectin, in Type 2 diabetic patients. Arterioscler. Thromb. Vasc. Biol. (2000) 20:1595-1599.
85. YANG WS, LEE WJ, FUNAHASHI T et al.: Weight reduction increases plasma levels of an adipose-derived ani-inflammatory protein, adiponectin. J. Clin. Endocrinol. Metab. (2001) 86:3815-3819.
86. WILLIAMSON DF, THOMPSON TJ, THUN M, FLANDERS D, PAMUK E, BYERS T: Intentional weight loss and mortality among overweight individuals with diabetes. Diabetes Care (2000) 23:1499-1504.
87. WEYER C, FUNAHASHI T, TANAKA S et al.: Hypoadiponectinemia in obesity and Type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J. Clin. Endocrinol. Metab. (2001) 86:1930-1935.
88. STEFAN N, VOZAROVA B, FUNAHASHI T et al.: Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes (2002) 51:1884-1888.
89. STEFAN N, BUNT JC, SALBE AD, FUNAHASHI T, MATSUZAWA Y, TATARANNI PA: Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J. Clin. Endocrinol. Metab. (2002) 87:4652-4656.
90. YAMAMOTO Y, HIROSE H, SAITO I et al.: Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin. Sci. (Lond.) (2002) 103:137-142.
91. KERSHAW EE, FLIER JS: Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. (2004) 89:2548-2556.
92. SCHULZE MB, RIMM EB, SHAI I, RIFAI N, HU FB: Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with Type 2 diabetes. Diabetes Care (2004) 27:1680-1687.
93. SCHULZE MB, SHAI I, RIMM EB, LI T, RIFAI N, HU FB: Adiponectin and future coronary heart disease events among men with Type 2 diabetes. Diabetes (2005) 54:534-539.
94. MANTZOROS CS, LI T, MANSON JE, MEIGS JB, HU FB: Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with Type 2 diabetes. J. Clin. Endocrinol. Metab. (2005) 90:4542-4548.
95. QI L, DORIA A, MANSON JE et al.: Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in patients with Type 2 diabetes. Diabetes (2006) 55:1512-1516.
96. PISCHON T, GIRMAN CJ, RIFAI N, HOTAMISLIGIL GS, RIMM EB: Association between dietary factors and plasma adiponectin concentrations in men. Am. J. Clin. Nutr. (2005) 81:780-786.
97. DAL MASO L, AUGUSTIN LS, KARALIS A et al.: Circulating adiponectin and endometrial cancer risk. J. Clin. Endocrinol. Metab. (2004) 89:1160-1163.
98. PETRIDOU E, MANTZOROS C, DESSYPRIS N et al.: Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J. Clin. Endocrinol. Metab. (2003) 88:993-997.
99. SOLIMAN PT, WU D, TORTOLERO-LUNA G et al.: Association between adiponectin, insulin resistance, and endometrial cancer. Cancer (2006) 106(11):2376-2381.
100. MANTZOROS C, PETRIDOU E, DESSYPRIS N et al.: Adiponectin and breast cancer risk. J. Clin. Endocrinol. Metab. (2004) 89:1102-1107.
101. MIYOSHI Y, FUNAHASHI T, KIHARA S et al.: Association of serum adiponectin levels with breast cancer risk. Clin. Cancer Res. (2003) 9:5699-5704.
102. CHEN DC, CHUNG YF, YEH YT et al.: Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. (2005) 237(1):109-114.
103. WEI EK, GIOVANNUCCI E, FUCHS CS, WILLETT WC, MANTZOROS CS: Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J. Natl. Cancer Inst. (2005) 97:1688-1694.
104. OTAKE S, TAKEDA H, SUZUKI Y et al.: Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance. Clin. Cancer Res. (2005) 11:3642-3646.
105. ISHIKAWA M, KITAYAMA J, KAZAMA S, HIRAMATSU T, HATANO K, NAGAWA H: Plasma adiponectin and gastric cancer. Clin. Cancer Res. (2005) 11:466-472.
106. FREEDLAND SJ, SOKOLL LJ, PLATZ FA et al.: Association between serum adiponectin, and pathological stage and grade in men undergoing radical prostatectomy. J. Urol. (2005) 174:1266-1270.
107. GOKTAS S, YILMAZ MI, CAGLAR K, SONMEZ A, KILIC S, BEDIR S: Prostate cancer and adiponectin. Urology (2005) 65:1168-1172.
108. PETRIDOU E, MANTZOROS CS, DESSYPRIS N, DIKALIOTI SK, TRICHOPOULOS D: Adiponectin in relation to childhood myeloblastic leukaemia. Br. J. Cancer (2006) 94:156-160.
109. KANG JH, LEE YY, YU BY et al.: Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch. Pharm. Res. (2005) 28:1263-1269.
110. DIEUDONNE MN, BUSSIERE M, DOS SE, LENEVEU MC, GIUDICELLI Y, PECQUERY R: Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem. Biophys. Res. Commun. (2006) 345(1):271-279.
111. BUB JD, MIYAZAKI T, IWAMOTO Y: Adiponectin as a growth inhibitor in prostate cancer cells. Biochem. Biophys. Res. Commun. (2006) 340:1158-1166.
112. BRAKENHIELM E, VEITONMAKI N, CAO R et al.: Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc. Natl. Acad. Sci. USA (2004) 101:2476-2481.
113. KUBOTA N, TERAUCHI Y, YAMAUCHI T et al.: Disruption of adiponectin causes insulin resistance and neointimal formation. J. Biol. Chem. (2002) 277:25863-25866.
114. COMBS TP, BERG AH, OBICI S, SCHERER PE, ROSSETTI L: Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J. Clin. Invest. (2001) 108:1875-1881.
115. HARVIE M, HOWELL A: Energy balance adiposity and breast cancer - energy restriction strategies for breast cancer prevention. Obes. Rev. (2006) 7:33-47.
116. DIEZ JJ, IGLESIAS P: The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur. J. Endocrinol. (2003) 148:293-300.
117. OKAMOTO Y, KIHARA S, OUCHI N et al.: Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation (2002) 106:2767-2770.
118. KAWANAMI D, MAEMURA K, TAKEDA N et al.: Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem. Biophys. Res. Commun. (2004) 314:415-419.
119. KOBASHI C, URAKAZE M, KISHIDA M et al.: Adiponectin inhibits endothelial synthesis of interleukin-8. Circ. Res. (2005) 97:1245-1252.
120. KUMADA M, KIHARA S, OUCHI N et al.: Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation (2004) 109:2046-2049.
121. WOLF AM, WOLF D, RUMPOLD H, ENRICH B, TILG H: Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem. Biophys. Res. Commun. (2004) 323:630-635.
122. OUCHI N, KIHARA S, ARITA Y et al.: Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-κB signaling through a cAMP-dependent pathway. Circulation (2000) 102:1296-1301.
123. FOLKMAN J: What is the evidence that tumors are angiogenesis dependent? J. Natl. Cancer Inst. (1990) 82:4-6.
124. CAO R, WU HL, VEITONMAKI N et al.: Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis. Proc. Natl. Acad. Sci. USA (1999) 96:5728-5733.
125. CHEN H, MONTAGNANI M, FUNAHASHI T, SHIMOMURA I, QUON MJ: Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J. Biol. Chem. (2003) 278:45021-45026.
126. OUCHI N, KOBAYASHI H, KIHARA S et al.: Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J. Biol. Chem. (2004) 279:1304-1309.
127. WANG Y, LAM KS, XU JY et al.: Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J. Biol. Chem. (2005) 280:18341-18347.
128. ARITA Y, KIHARA S, OUCHI N et al.: Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation (2002) 105:2893-2898.
129. YAMAUCHI T, KAMON J, WAKI H et al.: The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. (2001) 7:941-946.
130. LUO Z, SAHA AK, XIANG X, RUDERMAN NB: AMPK, the metabolic syndrome and cancer. Trends Pharmacol. Sci. (2005) 26:69-76.
131. INOKI K, ZHU T, GUAN KL: TSC2 mediates cellular energy response to control cell growth and survival. Cell (2003) 115:577-590.
132. CHENG SW, FRYER LG, CARLING D, SHEPHERD PR: Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status. J. Biol. Chem. (2004) 279:15719-15722.
133. CANTLEY LC, NEEL BG: New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/ AKT pathway. Proc. Natl. Acad. Sci. USA (1999) 96:4240-4245.
134. ZHOU BP, HUNG MC: Dysregulation of cellular signaling by HER2/neu in breast cancer. Semin. Oncol. (2003) 30:38-48.
135. KEFAS BA, CAI Y, LING Z et al.: AMP-activated protein kinase can induce apoptosis of insulin-producing MIN6 cells through stimulation of c-Jun-N-terminal kinase. J. Mol. Endocrinol. (2003) 30:151-161.
136. SAITOH M, NAGAI K, NAKAGAWA K, YAMAMURA T, YAMAMOTO S, NISHIZAKI T: Adenosine induces apoptosis in the human gastric cancer cells via an intrinsic pathway relevant to activation of AMP-activated protein kinase. Biochem. Pharmacol. (2004) 67:2005-2011.
137. MEISSE D, VAN DE CM, BEAULOYE C et al.: Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal kinase activation and apoptosis in liver cells. FEBS Lett. (2002) 526:38-42.
138. DAVIS RJ: Signal transduction by the JNK group of MAP kinases. Cell (2000) 103:239-252.
139. HIROSUMI J, TUNCMAN G, CHANG L et al.: A central role for JNK in obesity and insulin resistance. Nature (2002) 420:333-336.
140. LEVY DE, LEE CK: What does Stat3 do? J. Clin. Invest. (2002) 109:1143-1148.
141. RUDERMAN NB, CACICEDO JM, ITANI S et al.: Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes. Biochem. Soc. Trans. (2003) 31:202-206.
142. WANG CY, MAYO MW, KORNELUK RG, GOEDDEL DV, BALDWIN AS Jr: NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science (1998) 281:1680-1683.
143. PAJVANI UB, SCHERER PE: Adiponectin: systemic contributor to insulin sensitivity. Curr. Diab. Rep. (2003) 3:207-213.
144. BERG AH, COMBS TP, SCHERER PE: ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol. Metab. (2002) 13:84-89.