Structure, signalling and physiologic role of adiponectin-dietary and exercise-related variations

Current Medicinal Chemistry

Volumn 19, Issue 32, 2012, Pages 5427-5443

  Hickman, I J ^a,b   Whitehead, J P ^b  

^a PRINCESS ALEXANDRA HOSPITAL   (Australia)

^b MATER MEDICAL RESEARCH INSTITUTE   (Australia)

Author keywords

Adipokines; Cardiovascular disease; Diabetes; Inflammation; Receptors; Resistance; Signaling

Indexed keywords

4 HYDROXYNONENAL; ADIPONECTIN; ADIPONECTIN RECEPTOR 1; ADIPONECTIN RECEPTOR 2; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE KINASE; CALRETICULIN; CERAMIDE; CHAPERONE; COMPLEMENT COMPONENT C1Q; G PROTEIN COUPLED RECEPTOR; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; OMEGA 3 FATTY ACID; OSTEOCLAST DIFFERENTIATION FACTOR; OXIDOREDUCTASE; PROLINE; PROTEIN ERO 1LAPHA; PROTEIN ERP44; PROTEIN KINASE LKB1; PROTEIN T CADHERIN; RECEPTOR FOR ACTIVATED C KINASE 1; SORTILIN; SPHINGOSINE 1 PHOSPHATE; SPHINGOSINE KINASE; TAUROURSODEOXYCHOLIC ACID; THAPSIGARGIN; TRANSCRIPTION FACTOR FKHR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; AUTOPHAGY; CALORIC RESTRICTION; CARBOHYDRATE DIET; CONJUGATION; DIET SUPPLEMENTATION; DIETARY INTAKE; DISULFIDE BOND; DOWN REGULATION; EXERCISE; FAT INTAKE; GENE SILENCING; GLYCOSYLATION; HUMAN; HYDROXYLATION; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTRACELLULAR SIGNALING; LIPID METABOLISM; LIPID PEROXIDATION; LOSS OF FUNCTION MUTATION; MITOCHONDRIAL MEMBRANE; MUSCLE METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; OSTEOCLASTOGENESIS; PHYSICAL ACTIVITY; PROTEIN BINDING; PROTEIN BLOOD LEVEL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; SIALYLATION; UBIQUITINATION;

ADIPONECTIN; ANIMALS; DIET; EXERCISE; HUMANS; MOLECULAR CHAPERONES; PROTEIN CONFORMATION; SIGNAL TRANSDUCTION;

EID: 84870440691     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712803833155     Document Type: Article

References (198)

1. Zhang, Y.; Proenca, R.; Maffei, M.; Barone, M.; Leopold, L.; Friedman, J.M. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994, 372, 425-432.
2. Scherer, P.E.; Williams, S.; Fogliano, M.; Baldini, G.; Lodish, H.F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem., 1995, 270, 26746-26749.
3. Hu, E.; Liang, P.; Spiegelman, B.M. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem., 1996, 271, 10697-10703.
4. Nakano, Y.; Tobe, T. Choi-Miura, N.H.; 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.
5. 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.
6. Takemura, Y.; Walsh, K.; Ouchi, N. Adiponectin and cardiovascular inflammatory responses. Curr. Atheroscler. Rep., 2007, 9, 238-243.
7. Zhu, W.; Cheng, K.K.Y.; Vanhoutte, P.M.; Lam, K.S.L.; Xu, A. Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clinical Science, 2008, 114, 361-374.
8. Li, F.Y.; Cheng, K.K.; Lam, K.S.; Vanhoutte, P.M.; Xu, A. Cross-talk between adipose tissue and vasculature: role of adiponectin. Acta. Physiol. (Oxf), 2011, 203, 167-180.
9. Whitehead, J.; Richards, A.; Hickman, I.; Macdonald, G.; Prins, J. Adiponectin - a key adipokine in the metabolic syndrome. Diabetes, Obesity and Metabolism, 2006, 8, 264-280.
10. Kadowaki, T.; Yamauchi, T.; Kubota, N. The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett., 2008, 582, 74-80.
11. Kelesidis, I.; Kelesidis, T.; Mantzoros, C.S. Adiponectin and cancer: a systematic review. Br. J. Cancer., 2006, 94, 1221-1225.
12. Khandekar, M.J.; Cohen, P.; Spiegelman, B.M. Molecular mechanisms of cancer development in obesity. Nat. Rev. Cancer, 2011, 11, 886-895.
13. Zhou, M.; Xu, A.; Tam, P.K.H.; Lam, K.S.L.; Huang, B.; Liang, Y.; Lee, I.-K.; Wu, D.; Wang, Y. Upregulation of UCP2 by Adiponectin: The Involvement of Mitochondrial Superoxide and hnRNP K. PLoS One, 2012, 7, e32349.
14. Malone, J.H.; Oliver, B. Microarrays, deep sequencing and the true measure of the transcriptome. BMC Biol., 2011, 9, 34.
15. Fowler, J.A.; Lwin, S.T.; Drake, M.T.; Edwards, J.R.; Kyle, R.A.; Mundy, G.R.; Edwards, C.M. Host-derived adiponectin is tumor-suppressive and a novel therapeutic target for multiple myeloma and the associated bone disease. Blood, 2011.
16. Liu, M.; Liu, F. Transcriptional and post-translational regulation of adiponectin. Biochemical Journal, 2009, 425, 41-52.
17. Wang, Y.; Lam, K.S.; Yau, M.-h.; Xu, A., Post-translational modifications of adiponectin: mechanisms and functional implications. Biochemical Journal, 2008, 409, 623-633.
18. Simpson, F.; Whitehead, J.P. Adiponectin-It's all about the modifications. Int. J. Biochem. Cell. Biol., 2010, 42, 785-788.
19. Swarbrick, M.M.; Havel, P.J. Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. Metab. Syndr. Relat. Disord., 2008, 6, 87-102.
20. Pineiro, R.; Iglesias, M.J.; Gallego, R.; Raghay, K.; Eiras, S.; Rubio, J.; Dieguez, C.; Gualillo, O.; Gonzalez-Juanatey, J.R.; Lago, F. Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS Lett., 2005, 579, 5163-5169.
21. Skurk, C.; Wittchen, F.; Suckau, L.; Witt, H.; Noutsias, M.; Fechner, H.; Schultheiss, H.P.; Poller, W. Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy. Eur. Heart. J., 2008, 29, 1168-1180.
22. Amin, R.H.; Mathews, S.T.; Alli, A.; Leff, T. Endogenously Produced Adiponectin Protects Cardiomyocytes From Hypertrophy by a PPARγ-dependent Autocrine Mechanism. Am. J. Physiol. Heart Circ. Physiol., 2010.
23. 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.
24. Weyer, C.; Funahashi, T.; Tanaka, S.; Hotta, K.; Matsuzawa, Y.; Pratley, R.E.; Tataranni, P.A. Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resistance and Hyperinsulinemia. J. Clin. Endocrinol. Metab., 2001, 86, 1930-1935.
25. Spranger, J.; Kroke, A.; Mohlig, M.; Bergmann, M.M.; Ristow, M.; Boeing, H.; Pfeiffer, A.F. Adiponectin and protection against type 2 diabetes mellitus. Lancet, 2003, 361, 226-228.
26. Iwashima, Y.; Katsuya, T.; Ishikawa, K.; Ouchi, N.; Ohishi, M.; Sugimoto, K.; Fu, Y.; Motone, M.; Yamamoto, K.; Matsuo, A.; Ohashi, K.; Kihara, S.; Funahashi, T.; Rakugi, H.; Matsuzawa, Y.; Ogihara, T. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension, 2004, 43, 1318-1323.
27. Kern, P.A.; Di Gregorio, G.B.; Lu, T.; Rassouli, N.; Ranganathan, G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes, 2003, 52, 1779-1785.
28. Targher, G.; Bertolini, L.; Scala, L.; Poli, F.; Zenari, L.; Falezza, G. Decreased plasma adiponectin concentrations are closely associated with nonalcoholic hepatic steatosis in obese individuals. Clin. Endocrinol. (Oxf), 2004, 61, 700-703.
29. Cnop, M.; Havel, P.J.; Utzschneider, K.M.; Carr, D.B.; Sinha, M.K.; Boyko, E.J.; Retzlaff, B.M.; Knopp, R.H.; Brunzell, J.D.; Kahn, S.E. 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.
30. Koh, S.J.; Hyun, Y.J.; Choi, S.Y.; Chae, J.S.; Kim, J.Y.; Park, S.; Ahn, C.M.; Jang, Y.; Lee, J.H. Influence of age and visceral fat area on plasma adiponectin concentrations in women with normal glucose tolerance. Clin. Chim. Acta., 2008, 389, 45-50.
31. Kizer, J.R.; Arnold, A.M.; Strotmeyer, E.S.; Ives, D.G.; Cushman, M.; Ding, J.; Kritchevsky, S.B.; Chaves, P.H.; Hirsch, C.H.; Newman, A.B. Change in circulating adiponectin in advanced old age: determinants and impact on physical function and mortality. The Cardiovascular Health Study All Stars Study. J. Gerontol. A. Biol. Sci. Med. Sci., 2010, 65, 1208-1214.
32. Isobe, T.; Saitoh, S.; Takagi, S.; Takeuchi, H.; Chiba, Y.; Katoh, N.; Shimamoto, K. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur. J. Endocrinol., 2005, 153, 91-98.
33. Retnakaran, R.; Hanley, A.J.; Raif, N.; Connelly, P.W.; Sermer, M.; Zinman, B. Hypoadiponectinaemia in South Asian women during pregnancy: evidence of ethnic variation in adiponectin concentration. Diabetic Medicine, 2004, 21, 388-392.
34. Turer, A.T.; Khera, A.; Ayers, C.R.; Turer, C.B.; Grundy, S.M.; Vega, G.L.; Scherer, P.E. Adipose tissue mass and location affect circulating adiponectin levels. Diabetologia, 2011, 54, 2515-2524.
35. Zhu, N.; Pankow, J.S.; Ballantyne, C.M.; Couper, D.; Hoogeveen, R.C.; Pereira, M.; Duncan, B.B. Schmidt, M.I., High-molecular-weight adiponectin and the risk of type 2 diabetes in the ARIC study. J. Clin. Endocrinol. Metab., 2010, 95, 5097-5104.
36. Gao, H.; Salim, A.; Lee, J.; Tai, E.S.; van Dam, R.M. Can body fat distribution, adiponectin levels and inflammation explain differences in insulin resistance between ethnic Chinese, Malays and Asian Indians? Int. J. Obes. (Lond), 2011.
37. Waki, H.; Yamauchi, T.; Kamon, J.; Ito, Y.; Uchida, S.; Kita, S.; Hara, K.; Hada, Y.; Vasseur, F.; Froguel, P.; Kimura, S.; Nagai, R.; Kadowaki, T. Impaired multimerization of human adiponectin mutants associated with diabetes: Molecular structure and multimer formation of adiponectin. J. Biol. Chem., 2003, 278, 40352-40363.
38. Tsao, T.-S.; Tomas, E.; Murrey, H.E.; Hug, C.; Lee, D.H.; Ruderman, N.B.; Heuser, J.E.; Lodish, H.F. 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.
39. Pajvani, U.B.; Du, X.; Combs, T.P.; Berg, A.H.; Rajala, M.W.; Schulthess, T.; Engel, J.; Brownlee, M.; Scherer, P.E. Structure-Function Studies of the Adipocyte-secreted Hormone Acrp30/Adiponectin. IMPLICATIONS FOR METABOLIC REGULATION AND BIOACTIVITY. J. Biol. Chem., 2003, 278, 9073-9085.
40. Radjainia, M.; Wang, Y.; Mitra, A.K. Structural polymorphism of oligomeric adiponectin visualized by electron microscopy. J. Mol. Biol., 2008, 381, 419-430.
41. Whitehead, J.P.; Richards, A.A. Eds. Adiponectin. Wiley - VCH, 2010.
42. Kobayashi, H.; Ouchi, N.; Kihara, S.; Walsh, K.; Kumada, M.; Abe, Y.; Funahashi, T.; Matsuzawa, Y. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ. Res., 2004, 94, e27-31.
43. Fisher, F.F.; Trujillo, M.E.; Hanif, W.; Barnett, A.H.; McTernan, P.G.; Scherer, P.E.; Kumar, S. 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.
44. Lara-Castro, C.; Luo, N.; Wallace, P.; Klein, R.L.; Garvey, W.T. Adiponectin Multimeric Complexes and the Metabolic Syndrome Trait Cluster. Diabetes, 2006, 55, 249-259.
45. Hosogai, N.; Fukuhara, A.; Oshima, K.; Miyata, Y.; Tanaka, S.; Segawa, K.; Furukawa, S.; Tochino, Y.; Komuro, R.; Matsuda, M.; Shimomura, I. Adipose Tissue Hypoxia in Obesity and Its Impact on Adipocytokine Dysregulation. Diabetes, 2007, 56, 901-911.
46. Hotta, K.; Funahashi, T.; Bodkin, N.L.; Ortmeyer, H.K.; Arita, Y.; Hansen, B.C.; Matsuzawa, Y. Circulating Concentrations of the Adipocyte Protein Adiponectin Are Decreased in Parallel With Reduced Insulin Sensitivity During the Progression to Type 2 Diabetes in Rhesus Monkeys. Diabetes, 2001, 50, 1126-1133.
47. Nakashima, R.; Kamei, N.; Yamane, K.; Nakanishi, S.; Nakashima, A.; Kohno, N. Decreased total and high molecular weight adiponectin are independent risk factors for the development of type 2 diabetes in Japanese-Americans. J. Clin. Endocrinol. Metab., 2006, 91, 3873-3877.
48. Whitehead, J.P. Diabetes: New conductors for the peroxisome proliferatoractivated receptor gamma (PPARγ) orchestra. Int. J. Biochem. Cell. Biol., 2011, 43, 1071-1074.
49. Pajvani, U.B.; Hawkins, M.; Combs, T.P.; Rajala, M.W.; Doebber, T.; Berger, J.P.; Wagner, J.A.; Wu, M.; Knopps, A.; Xiang, A.H.; Utzschneider, K.M.; Kahn, S.E.; Olefsky, J.M.; Buchanan, T.A.; Scherer, P.E. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione -mediated improvement in insulin sensitivity. J. Biol. Chem., 2004, 279, 12152-12162.
50. Deepa, S.S.; Dong, L.Q. APPL1: Role in the Adiponectin Signaling and Beyond. Am. J. Physiol. Endocrinol. Metab., 2009, 296, E22-36.
51. Yamauchi, T.; Kadowaki, T. Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int. J. Obes., 2008, 32, S13-S18.
52. Yamauchi, T.; Kamon, J.; Ito, Y.; Tsuchida, A.; Yokomizo, T.; Kita, S.; Sugiyama, T.; Miyagishi, M.; Hara, K.; Tsunoda, M.; Murakami, K.; Ohteki, T.; Uchida, S.; Takekawa, S.; Waki, H.; Tsuno, N.H.; Shibata, Y.; Terauchi, Y.; Froguel, P.; Tobe, K.; Koyasu, S.; Taira, K.; Kitamura, T.; Shimizu, T.; Nagai, R.; Kadowaki, T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature, 2003, 423, 762-769.
53. Charlton, H.K.; Webster, J.; Kruger, S.; Simpson, F.; Richards, A.A.; Whitehead, J.P. ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling. Biochem. Biophys. Res. Commun., 2010, 392, 234-239.
54. Holland, W.L.; Miller, R.A.; Wang, Z.V.; Sun, K.; Barth, B.M.; Bui, H.H.; Davis, K.E.; Bikman, B.T.; Halberg, N.; Rutkowski, J.M.; Wade, M.R.; Tenorio, V.M.; Kuo, M.S.; Brozinick, J.T.; Zhang, B.B.; Birnbaum, M.J.; Summers, S.A.; Scherer, P.E. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat. Med., 2011, 17, 55-63.
55. Hug, C.; Wang, J.; Ahmad, N.S.; Bogan, J.S.; Tsao, T.-S.; Lodish, H.F. Tcadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc. Natl. Acad. Sci. U S A, 2004, 101, 10308-10313.
56. Hebbard, L.W.; Garlatti, M.; Young, L.J.T.; Cardiff, R.D.; Oshima, R.G.; Ranscht, B. T-cadherin Supports Angiogenesis and Adiponectin Association with the Vasculature in a Mouse Mammary Tumor Model. Cancer Res., 2008, 68, 1407-1416.
57. Denzel, M.S.; Scimia, M.C.; Zumstein, P.M.; Walsh, K.; Ruiz-Lozano, P.; Ranscht, B. T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J. Clin. Invest., 2010, 120, 4342-4352.
58. Takemura, Y.; Ouchi, N.; Shibata, R.; Aprahamian, T.; Kirber, M.T.; Summer, R.S.; Kihara, S.; Walsh, K. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J. Clin. Invest., 2007, 117, 375-386.
59. Ohashi, K.; Ouchi, N.; Sato, K.; Higuchi, A.; Ishikawa, T.-o.; Herschman, H.R.; Kihara, S.; Walsh, K. Adiponectin promotes revascularization of ischemic muscle through a COX-2 dependent mechanism. Mol. Cell. Biol., 2009, MCB.00126-00109.
60. Maruyama, S.; Shibata, R.; Ohashi, K.; Ohashi, T.; Daida, H.; Walsh, K.; Murohara, T.; Ouchi, N. Adiponectin Ameliorates Doxorubicin-induced Cardiotoxicity through Akt Protein-dependent Mechanism. J. Biol. Chem., 2011, 286, 32790-32800.
61. Shapiro, L.; Scherer, P.E. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Current Biology, 1998, 8, 335-340.
62. Richards, A.A.; Colgrave, M.L.; Jialiang, Z.; Webster, J.; Simpson, F.; Preston, E.; Wilks, D.; Hoehn, K.L.; Stephenson, M.; Macdonald, G.A.; Prins, J.B.; Cooney, G.J.; Xu, A.; Whitehead, J.P. Sialic Acid Modification of Adiponectin Is Not Required for Multimerization or Secretion but Determines Half-Life in Circulation. Mol. Endocrinol., 2010, 24, 229-239.
63. Schraw, T.; Wang, Z.V.; Halberg, N.; Hawkins, M.; Scherer, P.E. Plasma adiponectin complexes have distinct biochemical characteristics. Endocrinology, 2008, 149, 2270-2282.
64. Wang, Z.V.; Schraw, T.D.; Kim, J.-Y.; Khan, T.; Rajala, M.W.; Follenzi, A.; Scherer, P.E. Secretion of the Adipocyte-Specific Secretory Protein Adiponectin Critically Depends on Thiol-Mediated Protein Retention. Mol. Cell. Biol., 2007, 27, 3716-3731.
65. Liu, M.; Zhou, L.; Xu, A.; Lam, K.S.; Wetzel, M.D.; Xiang, R.; Zhang, J.; Xin, X.; Dong, L.Q.; Liu, F. A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization. Proc. Natl. Acad. Sci. U S A, 2008, 105, 18302-18307.
66. Frizzell, N.; Rajesh, M.; Jepson, M.J.; Nagai, R.; Carson, J.A.; Thorpe, S.R.; Baynes, J.W. Succination of thiol groups in adipose tissue proteins in diabetes:Succination inhibits polymerizaton and secretion of adiponectin. J. Biol. Chem., 2009, M109.019257.
67. Richards, A.A.; Stephens, T.; Charlton, H.K.; Jones, A.; Macdonald, G.A.; Prins, J.B.; Whitehead, J.P. Adiponectin multimerisation is dependent on conserved lysines in the collagenous domain: Evidence for regulation of multimerisation by alterations in post-translational modifications. Mol. Endocrinol., 2006, 20, 1673-1687.
68. Wang, Y.; Xu, A.; Knight, C.; Xu, L.Y.; Cooper, G.J.S. Hydroxylation and Glycosylation of the Four Conserved Lysine Residues in the Collagenous Domain of Adiponectin. POTENTIAL ROLE IN THE MODULATION OF ITS INSULIN-SENSITIZING ACTIVITY. J. Biol. Chem., 2002, 277, 19521-19529.
69. Wang, Y.; Lam, K.S.L.; Chan, L.; Chan, K.W.; Lam, J.B.B.; Lam, M.C.; Hoo, R.C.L.; Mak, W.W.N.; Cooper, G.J.S.; Xu, A. Posttranslational modifications on the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high-molecularweight oligomeric complex. J. Biol. Chem., 2006, 281, (24), 16391-16400.
70. Wang, C.; Luosujarvi, H.; Heikkinen, J.; Risteli, M.; Uitto, L.; Myllyla, R. The third activity for lysyl hydroxylase 3: galactosylation of hydroxylysyl residues in collagens in vitro. Matrix Biol., 2002, 21, 559-566.
71. Afkhami-Ardekani, M.; Shojaoddiny-Ardekani, A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. The Indian journal of medical research, 2007, 126, 471-474.
72. Rose, F.J.; Webster, J.; Barry, J.B.; Phillips, L.K.; Richards, A.A.; Whitehead, J.P. Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes. Diabetes Obes. Metab., 2010, 12, 1084-1089.
73. Soares, A.F.; Guichardant, M.; Cozzone, D.; Bernoud-Hubac, N.; Bouzaidi-Tiali, N.; Lagarde, M.; Geloen, A. Effects of oxidative stress on adiponectin secretion and lactate production in 3T3-L1 adipocytes. Free Radic. Biol. Med., 2005, 38, 882-889.
74. Wang, Z.; Dou, X.; Gu, D.; Shen, C.; Yao, T.; Nguyen, V.; Braunschweig, C.; Song, Z. 4-Hydroxynonenal differentially regulates adiponectin gene expression and secretion via activating PPARgamma and accelerating ubiquitin-proteasome degradation. Mol. Cell. Endocrinol., 2012, 349, 222-231.
75. Tang, H.; Sebastian, B.M.; Axhemi, A.; Chen, X.; Hillian, A.D.; Jacobsen, D.W.; Nagy, L.E. Ethanol-Induced Oxidative Stress via the CYP2E1 Pathway Disrupts Adiponectin Secretion from Adipocytes. Alcohol Clin. Exp. Res., 2012, 36, 214-222.
76. Jungtrakoon, P.; Plengvidhya, N.; Tangjittipokin, W.; Chimnaronk, S.; Salaemae, W.; Chongjaroen, N.; Chanprasert, K.; Sujjitjoon, J.; Srisawat, C.; Yenchitsomanus, P.T. Novel adiponectin variants identified in type 2 diabetic patients reveal multimerization and secretion defects. PLoS One, 2011, 6, e26792.
77. Xie, L.; O'Reilly, C.P.; Chapes, S.K.; Mora, S. Adiponectin and leptin are secreted through distinct trafficking pathways in adipocytes. Biochim. Biophys. Acta., 2008, 1782, 99-108.
78. Qiang, L.; Wang, H.; Farmer, S.R. Adiponectin Secretion Is Regulated by SIRT1 and the Endoplasmic Reticulum Oxidoreductase Ero1-L{alpha}. Mol. Cell. Biol., 2007, 27, 4698-4707.
79. Zhou, L.; Liu, M.; Zhang, J.; Chen, H.; Dong, L.Q.; Liu, F. DsbA-L Alleviates Endoplasmic Reticulum Stress-induced Adiponectin Downregulation. Diabetes, 2010, 59, 2809-2816.
80. Baur, J.A.; Pearson, K.J.; Price, N.L.; Jamieson, H.A.; Lerin, C.; Kalra, A.; Prabhu, V.V.; Allard, J.S.; Lopez-Lluch, G.; Lewis, K.; Pistell, P.J.; Poosala, S.; Becker, K.G.; Boss, O.; Gwinn, D.; Wang, M.; Ramaswamy, S.; Fishbein, K.W.; Spencer, R.G.; Lakatta, E.G.; Le Couteur, D.; Shaw, R.J.; Navas, P.; Puigserver, P.; Ingram, D.K.; de Cabo, R.; Sinclair, D.A. Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 2006, 444, 337-342.
81. Wang, A.; Liu, M.; Liu, X.; Dong, L.Q.; Glickman, R.D.; Slaga, T.J.; Zhou, Z.; Liu, F. Up-regulation of adiponectin by resveratrol: the essential roles of the Akt/FOXO1 and AMP-activated protein kinase signaling pathways and DsbA-L. J. Biol. Chem., 2011, 286, 60-66.
82. Tran, K.-V.; Gealekman, O.; Frontini, A.; Zingaretti, Maria C.; Morroni, M.; Giordano, A.; Smorlesi, A.; Perugini, J.; De Matteis, R.; Sbarbati, A.; Corvera, S.; Cinti, S. The Vascular Endothelium of the Adipose Tissue Gives Rise to Both White and Brown Fat Cells. Cell Metab., 2012, 15, 222-229.
83. Dutchak, Paul A.; Katafuchi, T.; Bookout, Angie L.; Choi, Jang H.; Yu, Ruth T.; Mangelsdorf, David J.; Kliewer, Steven A. Fibroblast Growth Factor-21 Regulates PPARγ Activity and the Antidiabetic Actions of Thiazolidinediones. Cell, 2012, 148, 556-567.
84. Theodoratos, A.; Blackburn, A.C.; Coggan, M.; Cappello, J.; Larter, C.Z.; Matthaei, K.I.; Board, P.G. The impact of glutathione transferase kappa deficiency on adiponectin multimerisation in vivo. Int. J. Obes. (Lond), 2012.
85. Nishizawa, H.; Shimomura, I.; Kishida, K.; Maeda, N.; Kuriyama, H.; Nagaretani, H.; Matsuda, M.; Kondo, H.; Furuyama, N.; Kihara, S.; Nakamura, T.; Tochino, Y.; Funahashi, T.; Matsuzawa, Y. Androgens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein. Diabetes, 2002, 51, 2734-2741.
86. Xu, A.; Chan, K.W.; Hoo, R.L.; Wang, Y.; Tan, K.C.; Zhang, J.; Chen, B.; Lam, M.C.; Tse, C.; Cooper, G.J.; Lam, K.S. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J. Biol. Chem., 2005, 280, 18073-18080.
87. Karki, S.; Chakrabarti, P.; Huang, G.; Wang, H.; Farmer, S.R.; Kandror, K.V. The multi-level action of Fatty acids on adiponectin production by fat cells. PLoS One, 2011, 6, e28146.
88. Combs, T.P.; Pajvani, U.B.; Berg, A.H.; Lin, Y.; Jelicks, L.A.; Laplante, M.; Nawrocki, A.R.; Rajala, M.W.; Parlow, A.F.; Cheeseboro, L.; Ding, Y.Y.; Russell, R.G.; Lindemann, D.; Hartley, A.; Baker, G.R.; Obici, S.; Deshaies, Y.; Ludgate, M.; Rossetti, L.; Scherer, P.E. A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity. Endocrinology, 2004, 145, 367-383.
89. Narasimhan, M.L.; Coca, M.A.; Jin, J.; Yamauchi, T.; Ito, Y.; Kadowaki, T.; Kim, K.K.; Pardo, J.M.; Damsz, B.; Hasegawa, P.M. Osmotin Is a Homolog of Mammalian Adiponectin and Controls Apoptosis in Yeast through a Homolog of Mammalian Adiponectin Receptor. Mol. Cell., 2005, 17, 171-180.
90. Lee, M.H.; Klein, R.L.; El-Shewy, H.M.; Luttrell, D.K.; Luttrell, L.M. The Adiponectin Receptors AdipoR1 and AdipoR2 Activate ERK1/2 through a Src/Ras-Dependent Pathway and Stimulate Cell Growth. Biochemistry, 2008, 47, 11682-11692.
91. Kosel, D.; Heiker, J.T.; Juhl, C.; Wottawah, C.M.; Bluher, M.; Morl, K.; Beck-Sickinger, A.G. Dimerization of adiponectin receptor 1 is inhibited by adiponectin. J. Cell. Sci., 2010, 123, 1320-1328.
92. Rasmussen, M.S.; Lihn, A.S.; Pedersen, S.B.; Bruun, J.M.; Rasmussen, M.; Richelsen, B. Adiponectin receptors in human adipose tissue: effects of obesity, weight loss, and fat depots. Obesity (Silver Spring), 2006, 14, 28-35.
93. Tsuchida, A.; Yamauchi, T.; Ito, Y.; Hada, Y.; Maki, T.; Takekawa, S.; Kamon, J.; Kobayashi, M.; Suzuki, R.; Hara, K.; Kubota, N.; Terauchi, Y.; Froguel, P.; Nakae, J.; Kasuga, M.; Accili, D.; Tobe, K.; Ueki, K.; Nagai, R.; Kadowaki, T. Insulin/Foxo1 Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity. J. Biol. Chem., 2004, 279, 30817-30822.
94. Bluher, M.; Fasshauer, M.; Kralisch, S.; Schon, M.R.; Krohn, K.; Paschke, R. Regulation of adiponectin receptor R1 and R2 gene expression in adipocytes of C57BL/6 mice. Biochem. Biophys. Res. Commun., 2005, 329, 1127-1132.
95. Li, W.; Tonelli, J.; Kishore, P.; Owen, R.; Goodman, E.; Scherer, P.E.; Hawkins, M. Insulin-sensitizing effects of thiazolidinediones are not linked to adiponectin receptor expression in human fat or muscle. Am. J. Physiol. Endocrino.l Metab., 2007, 292, E1301-1307.
96. Tsuchida, A.; Yamauchi, T.; Takekawa, S.; Hada, Y.; Ito, Y.; Maki, T.; Kadowaki, T. Peroxisome Proliferator-Activated Receptor (PPAR){alpha} 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.
97. Kaltenbach, S.; Staiger, H.; Weisser, M.; Haas, C.; Stumvoll, M.; Machicao, F.; Haring, H.U. Adiponectin receptor gene expression in human skeletal muscle cells is not regulated by fibrates and thiazolidinediones. Int. J. Obes. (Lond), 2005, 29, 760-765.
98. Yamauchi, T.; Nio, Y.; Maki, T.; Kobayashi, M.; Takazawa, T.; Iwabu, M.; Okada-Iwabu, M.; Kawamoto, S.; Kubota, N.; Kubota, T.; Ito, Y.; Kamon, J.; Tsuchida, A.; Kumagai, K.; Kozono, H.; Hada, Y.; Ogata, H.; Tokuyama, K.; Tsunoda, M.; Ide, T.; Murakami, K.; Awazawa, M.; Takamoto, I.; Froguel, P.; Hara, K.; Tobe, K.; Nagai, R.; Ueki, K.; Kadowaki, T. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat. Med., 2007, 13, 332-339.
99. Bjursell, M.; Ahnmark, A.; Bohlooly-Y, M.; William-Olsson, L.; Rhedin, M.; Peng, X.-R.; Ploj, K.; Gerdin, A.-K.; Arnerup, G.; Elmgren, A.; Berg, A.-L.; Oscarsson, J.; Linden, D. Opposing Effects of Adiponectin Receptors 1 and 2 on Energy Metabolism. Diabetes, 2007, 56, 583-593.
100. Liu, Y.; Michael, M.D.; Kash, S.; Bensch, W.R.; Monia, B.P.; Murray, S.F.; Otto, K.A.; Syed, S.K.; Bhanot, S.; Sloop, K.W.; Sullivan, J.M.; Reifel-Miller, A. Deficiency of Adiponectin Receptor 2 Reduces Diet-Induced Insulin Resistance but Promotes Type 2 Diabetes. Endocrinology, 2007, 148, 683-692.
101. Holland, W.L.; Brozinick, J.T.; Wang, L.P.; Hawkins, E.D.; Sargent, K.M.; Liu, Y.; Narra, K.; Hoehn, K.L.; Knotts, T.A.; Siesky, A.; Nelson, D.H.; Karathanasis, S.K.; Fontenot, G.K.; Birnbaum, M.J.; Summers, S.A. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-,and obesity-induced insulin resistance. Cell Metab., 2007, 5, 167-179.
102. Holland, W.L.; Scherer, P.E. PAQRs: a counteracting force to ceramides? Mol. Pharmacol., 2009, 75, 740-743.
103. Mao, X.; Hong, J.Y.; Dong, L.Q. The adiponectin signaling pathway as a novel pharmacological target. Mini Rev. Med. Chem., 2006, 6, 1331-1340.
104. Mao, X.; Kikani, C.K.; Riojas, R.A.; Langlais, P.; Wang, L.; Ramos, F.J.; Fang, Q.; Christ-Roberts, C.Y.; Hong, J.Y.; Kim, R.Y.; Liu, F.; Dong, L.Q. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat. Cell Biol., 2006, 8, 516-523.
105. Cheng, K.K.; Lam, K.S.; Wang, Y.; Yu, H.; Carling, D.; Wu, D.; Wong, C.; Xu, A. Adiponectin-induced eNOS activation and Nitric Oxide Production are Mediated by APPL1 in Endothelial Cells. Diabetes, 2007, 56, 1387-1394.
106. Saito, T.; Jones, C.C.; Huang, S.; Czech, M.P.; Pilch, P.F. The interaction of AKT with APPL1 is required for insulin-stimulated Glut4 translocation. J. Biol. Chem., 2007, 282, 32280-32287.
107. Tu, Q.; Zhang, J.; Dong, L.Q.; Saunders, E.; Luo, E.; Tang, J.; Chen, J. Adiponectin inhibits osteoclastogenesis and bone resorption via APPL1-mediated suppression of Akt1. J. Biol. Chem., 2011, 286, 12542-12553.
108. Wang, C.; Xin, X.; Xiang, R.; Ramos, F.J.; Liu, M.; Lee, H.J.; Chen, H.; Mao, X.; Kikani, C.K.; Liu, F.; Dong, L.Q. "Yin-Yang" regulation of adiponectin signaling by APPL isoforms in muscle cells. J. Biol. Chem., 2009, 284, 31608-31615.
109. Holmes, R.M.; Yi, Z.; De Filippis, E.; Berria, R.; Shahani, S.; Sathyanarayana, P.; Sherman, V.; Fujiwara, K.; Meyer, C.; Christ-Roberts, C.; Hwang, H.; Finlayson, J.; Dong, L.Q.; Mandarino, L.J.; Bajaj, M. Increased abundance of the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1) in patients with obesity and type 2 diabetes: evidence for altered adiponectin signalling. Diabetologia, 2011, 54, 2122-2131.
110. Bruce, C.R.; Mertz, V.A.; Heigenhauser, G.J.; Dyck, D.J. The stimulatory effect of globular adiponectin on insulin-stimulated glucose uptake and fatty acid oxidation is impaired in skeletal muscle from obese subjects. Diabetes, 2005, 54, 3154-3160.
111. Chen, M.B.; McAinch, A.J.; Macaulay, S.L.; Castelli, L.A.; O'Brien, P.E.; Dixon, J.B.; Cameron-Smith, D.; Kemp, B.E.; Steinberg, G.R. Impaired Activation of AMP-Kinase and Fatty Acid Oxidation by Globular Adiponectin in Cultured Human Skeletal Muscle of Obese Type 2 Diabetics. J. Clin. Endocrinol. Metab., 2005, 90, 3665-3672.
112. Mullen, K.L.; Pritchard, J.; Ritchie, I.; Snook, L.A.; Chabowski, A.; Bonen, A.; Wright, D.; Dyck, D.J. Adiponectin resistance precedes the accumulation of skeletal muscle lipids and insulin resistance in high-fat-fed rats. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2009, 296, R243-251.
113. Xu, Y.; Wang, N.; Ling, F.; Li, P.; Gao, Y. Receptor for activated C-kinase 1, a novel binding partner of adiponectin receptor 1. Biochem Biophys Res Commun, 2009, 378, 95-98.
114. Heiker, J.T.; Wottawah, C.M.; Juhl, C.; Kosel, D.; Morl, K.; Beck-Sickinger, A.G. Protein kinase CK2 interacts with adiponectin receptor 1 and participates in adiponectin signaling. Cell Signal., 2009, 21, 936-942.
115. Juhl, C.; Morl, K.; Beck-Sickinger, A.G. Adiponectin receptor 1 interacts with both subunits of protein kinase CK2. Mol. Cell. Biochem., 2011, 356, 185-189.
116. Fryer, L.G.; Parbu-Patel, A.; Carling, D. The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J. Biol. Chem., 2002, 277, 25226-25232.
117. Sanders, M.J.; Grondin, P.O.; Hegarty, B.D.; Snowden, M.A.; Carling, D. Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochemical J., 2007, 403, 139-148.
118. Deepa, S.S.; Zhou, L.; Ryu, J.; Wang, C.; Mao, X.; Li, C.; Zhang, N.; Musi, N.; Defronzo, R.A.; Liu, F.; Dong, L.Q. APPL1 Mediates Adiponectin-Induced LKB1 Cytosolic Localization Through the PP2A-PKCZ Signaling Pathway. Mol. Endocrinol., 2011, 25, 1773-1785.
119. Zhou, L.; Deepa, S.S.; Etzler, J.C.; Ryu, J.; Mao, X.; Fang, Q.; Liu, D.D.; Torres, J.M.; Jia, W.; Lechleiter, J.D.; Liu, F.; Dong, L.Q. Adiponectin activates AMPK in muscle cells via APPL1/LKB1- and PLC/Ca2+/CaMKKdependent pathways. J. Biol. Chem., 2009, 284, 22426-22435.
120. Iwabu, M.; Yamauchi, T.; Okada-Iwabu, M.; Sato, K.; Nakagawa, T.; Funata, M.; Yamaguchi, M.; Namiki, S.; Nakayama, R.; Tabata, M.; Ogata, H.; Kubota, N.; Takamoto, I.; Hayashi, Y.K.; Yamauchi, N.; Waki, H.; Fukayama, M.; Nishino, I.; Tokuyama, K.; Ueki, K.; Oike, Y.; Ishii, S.; Hirose, K.; Shimizu, T.; Touhara, K.; Kadowaki, T. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature, 2010, 464, 1313-1319.
121. Ouedraogo, R.; Wu, X.; Xu, S.-Q.; Fuchsel, L.; Motoshima, H.; Mahadev, K.; Hough, K.; Scalia, R.; Goldstein, B.J. Adiponectin Suppression of High-Glucose-Induced Reactive Oxygen Species in Vascular Endothelial Cells: Evidence for Involvement of a cAMP Signaling Pathway. Diabetes, 2006, 55, 1840-1846.
122. Wu, X.; Mahadev, K.; Fuchsel, L.; Ouedraogo, R.; Xu, S.-q.; Goldstein, B.J. Adiponectin Suppresses IkB Kinase Activation Induced by Tumor Necrosis Factor-α or High Glucose in Endothelial Cells: Role of cAMP and AMP Kinase Signaling. Am. J. Physiol. Endocrinol. Metab., 2007, 293, E1836-1844.
123. Ling, H.; Waterworth, D.M.; Stirnadel, H.A.; Pollin, T.I.; Barter, P.J.; Kesaniemi, Y.A.; Mahley, R.W.; McPherson, R.; Waeber, G.; Bersot, T.P.; Cohen, J.C.; Grundy, S.M.; Mooser, V.E.; Mitchell, B.D. Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study. Obesity (Silver Spring), 2009, 17, 737-744.
124. Jee, S.H.; Sull, J.W.; Lee, J.E.; Shin, C.; Park, J.; Kimm, H.; Cho, E.Y.; Shin, E.S.; Yun, J.E.; Park, J.W.; Kim, S.Y.; Lee, S.J.; Jee, E.J.; Baik, I.; Kao, L.; Yoon, S.K.; Jang, Y.; Beaty, T.H. Adiponectin concentrations: a genomewide association study. Am. J. Hum. Genet., 2010, 87, 545-552.
125. Wu, Y.; Li, Y.; Lange, E.M.; Croteau-Chonka, D.C.; Kuzawa, C.W.; McDade, T.W.; Qin, L.; Curocichin, G.; Borja, J.B.; Lange, L.A.; Adair, L.S.; Mohlke, K.L. Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ. Hum. Mol. Genet., 2010, 19, 4955-4964.
126. Fava, C.; Danese, E.; Montagnana, M.; Sjogren, M.; Almgren, P.; Guidi, G.C.; Hedblad, B.; Engstrom, G.; Lechi, A.; Minuz, P.; Melander, O. A variant upstream of the CDH13 adiponectin receptor gene and metabolic syndrome in Swedes. Am. J. Cardiol., 2011, 108, 1432-1437.
127. Chung, C.M.; Lin, T.H.; Chen, J.W.; Leu, H.B.; Yang, H.C.; Ho, H.Y.; Ting, C.T.; Sheu, S.H.; Tsai, W.C.; Chen, J.H.; Lin, S.J.; Chen, Y.T.; Pan, W.H. A Genome-Wide Association Study Reveals a Quantitative Trait Locus of Adiponectin on CDH13 That Predicts Cardiometabolic Outcomes. Diabetes, 2011, 60, 2417-2423.
128. Morisaki, H.; Yamanaka, I.; Iwai, N.; Miyamoto, Y.; Kokubo, Y.; Okamura, T.; Okayama, A.; Morisaki, T. CDH13 gene coding t-cadherin influences variations in plasma adiponectin levels in the Japanese population. Hum. Mutat., 2012, 33, 402-410.
129. Qi, Y.; Takahashi, N.; Hileman, S.M.; Patel, H.R.; Berg, A.H.; Pajvani, U.B.; Scherer, P.E.; Ahima, R.S. Adiponectin acts in the brain to decrease body weight. Nat. Med., 2004, 10, 524-529.
130. Coope, A.; Milanski, M.; Araújo, E.P.; Tambascia, M.; Saad, M.J.A.; Geloneze, B.; Velloso, L.A. AdipoR1 mediates the anorexigenic and insulin/leptin-like actions of adiponectin in the hypothalamus. FEBS Lett., 2008, 582, 1471-1476.
131. Kubota, N.; Yano, W.; Kubota, T.; Yamauchi, T.; Itoh, S.; Kumagai, H.; Kozono, H.; Takamoto, I.; Okamoto, S.; Shiuchi, T.; Suzuki, R.; Satoh, H.; Tsuchida, A.; Moroi, M.; Sugi, K.; Noda, T.; Ebinuma, H.; Ueta, Y.; Kondo, T.; Araki, E.; Ezaki, O.; Nagai, R.; Tobe, K.; Terauchi, Y.; Ueki, K.; Minokoshi, Y.; Kadowaki, T. Adiponectin Stimulates AMP-Activated Protein Kinase in the
132. Neumeier, M.; Weigert, J.; Buettner, R.; Wanninger, J.; Schaffler, A.; Muller, A.M.; Killian, S.; Sauerbruch, S.; Schlachetzki, F.; Steinbrecher, A.; Aslanidis, C.; Scholmerich, J.; Buechler, C. Detection of adiponectin in cerebrospinal fluid in humans. Am. J. Physiol. Endocrinol. Metab., 2007, 293, E965-969.
133. Kusminski, C.M.; McTernan, P.G.; Schraw, T.; Kos, K.; O'Hare J, P.; Ahima, R.; Kumar, S.; Scherer, P.E. Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum. Diabetologia, 2007, 50, 634-642.
134. Behre, C.J., Adiponectin: Saving the starved and the overfed. Med. Hypotheses., 2007, 69, 1290-1292.
135. L'Abbate, A.; Neglia, D.; Vecoli, C.; Novelli, M.; Ottaviano, V.; Baldi, S.; Barsacchi, R.; Paolicchi, A.; Masiello, P.; Drummond, G.S.; McClung, J.A.; Abraham, N.G. Beneficial effect of heme oxygenase-1 expression on myocardial ischemia-reperfusion involves an increase in adiponectin in mildly diabetic rats. Am. J. Physiol. Heart. Circ. Physiol., 2007, 293, H3532-3541.
136. Li, M.; Kim, D.H.; Tsenovoy, P.L.; Peterson, S.J.; Rezzani, R.; Rodella, L.F.; Aronow, W.S.; Ikehara, S.; Abraham, N.G. Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance. Diabetes, 2008, 57, 1526-1535.
137. Burgess, A.; Li, M.; Vanella, L.; Kim, D.H.; Rezzani, R.; Rodella, L.; Sodhi, K.; Canestraro, M.; Martasek, P.; Peterson, S.J.; Kappas, A.; Abraham, N.G. Adipocyte Heme Oxygenase-1 Induction Attenuates Metabolic Syndrome in Both Male and Female Obese Mice. Hypertension, 2010, 56, 1124-1130.
138. Mandal, P.; Park, P.H.; McMullen, M.R.; Pratt, B.T.; Nagy, L.E. The antiinflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat Kupffer cells. Hepatology, 2010, 51, 1420-1429.
139. Mandal, P.; Pritchard, M.T.; Nagy, L.E. Anti-inflammatory pathways and alcoholic liver disease: role of an adiponectin/interleukin-10/heme oxygenase-1 pathway. World J. Gastroenterol., 2010, 16, 1330-1336.
140. Salamone, F.; Li Volti, G. Targeting heme oxygenase/adiponectin axis for chronic hepatitis C treatment. Hepatology, 2010, 52, 801.
141. Cao, J.; Sodhi, K.; Puri, N.; Monu, S.R.; Rezzani, R.; Abraham, N.G. High fat diet enhances cardiac abnormalities in SHR rats: Protective role of heme oxygenase-adiponectin axis. Diabetol. Metab. Syndr., 2011, 3, 37.
142. Burgess, A.P.; Vanella, L.; Bellner, L.; Gotlinger, K.; Falck, J.R.; Abraham, N.G.; Schwartzman, M.L.; Kappas, A. Heme oxygenase (HO-1) rescue of adipocyte dysfunction in HO-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin. Cell Physiol. Biochem., 2012, 29, 99-110.
143. Cheng, C.F.; Lian, W.S.; Chen, S.H.; Lai, P.F.; Li, H.F.; Lan, Y.F.; Cheng, W.T.; Lin, H. Protective effects of adiponectin against renal ischemiareperfusion injury via prostacyclin-PPARα-heme oxygenase-1 signaling pathway. J. Cell Physiol., 2012, 227, (1), 239-249.
144. Silva, F.M.; de Almeida, J.C.; Feoli, A.M. Effect of diet on adiponectin levels in blood. Nutr. Rev., 2011, 69, 599-612.
145. Pischon, T.; Girman, C.J.; Rifai, N.; Hotamisligil, G.S.; Rimm, E.B., Association between dietary factors and plasma adiponectin concentrations in men. The American journal of clinical nutrition, 2005, 81, 780-786.
146. Mostad, I.L.; Qvigstad, E.; Bjerve, K.S.; Grill, V.E., Effects of a 3-day lowfat diet on metabolic control, insulin sensitivity, lipids and adipocyte hormones in Norwegian subjects with hypertriacylglycerolaemia and type 2 diabetes. Scandinavian journal of clinical and laboratory investigation, 2004, 64, 565-574.
147. Berk, E.S.; Kovera, A.J.; Boozer, C.N.; Pi-Sunyer, F.X.; Johnson, J.A.; Albu, J.B., Adiponectin levels during low- and high-fat eucaloric diets in lean and obese women. Obesity research, 2005, 13, 1566-1571.
148. Tan, H.Y.; Rand, J.S.; Morton, J.M.; Fleeman, L.M.; Armstrong, P.J.; Coradini, M.; Ishioka, K.; Verkest, K.R.; Richards, A.A.; Rawlings, J.M.; Rose, F.J.; Whitehead, J.P., Adiponectin profiles are affected by chronic and acute changes in carbohydrate intake in healthy cats. Gen Comp Endocrinol, 2011, 172, 468-474.
149. Kasim-Karakas, S.E.; Tsodikov, A.; Singh, U.; Jialal, I., Responses of inflammatory markers to a lowfat, high-carbohydrate diet: effects of energy intake. The American journal of clinical nutrition, 2006, 83, 774779.
150. DeFronzo, R.A.; Tobin, J.D.; Andres, R., Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol, 1979, 237, E214-223.
151. Elisha, B.; Karelis, A.D.; Imbeault, P.; Rabasa-Lhoret, R., Effects of acute hyperinsulinaemia on total and high-molecular-weight adiponectin concentration in metabolically healthy but obese postmenopausal women: a Montreal-Ottawa New Emerging Team (MONET) study. Diabetes Metab, 2010, 36, 319-321.
152. Drapeau, S.; Doucet, E.; Rabasa-Lhoret, R.; Brochu, M.; Prud'homme, D.; Imbeault, P., Improvement in insulin sensitivity by weight loss does not affect hyperinsulinemia-mediated reduction in total and high molecular weight adiponectin: a MONET study. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 2011, 36, 191-200.
153. Qiao, L.; Shao, J., SIRT1 Regulates Adiponectin Gene Expression through Foxo1-C/Enhancer-binding Protein {alpha} Transcriptional Complex. J. Biol. Chem., 2006, 281, 39915-39924.
154. Semple, R.K.; Halberg, N.H.; Burling, K.; Soos, M.A.; Schraw, T.; Luan, J.; Cochran, E.K.; Dunger, D.B.; Wareham, N.J.; Scherer, P.E.; Gorden, P.; O'Rahilly, S., Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodies. Diabetes, 2007, 56, 17121717.
155. Fasshauer, M.; Klein, J.; Neumann, S.; Eszlinger, M.; Paschke, R., Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun, 2002, 290, 1084-1089.
156. Flachs, P.; Rossmeisl, M.; Bryhn, M.; Kopecky, J., Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clinical science, 2009, 116, 1-16.
157. Fernandez-Real, J.M.; Vendrell, J.; Ricart, W., Circulating adiponectin and plasma fatty acid profile. Clinical chemistry, 2005, 51, 603-609.
158. Arterburn, L.M.; Hall, E.B.; Oken, H., Distribution, interconversion, and dose response of n-3 fatty acids in humans. The American journal of clinical nutrition, 2006, 83, 1467S-1476S.
159. Duda, M.K.; O'Shea, K.M.; Tintinu, A.; Xu, W.; Khairallah, R.J.; Barrows, B.R.; Chess, D.J.; Azimzadeh, A.M.; Harris, W.S.; Sharov, V.G.; Sabbah, H.N.; Stanley, W.C., Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction. Cardiovascular research, 2009, 81, 319-327.
160. Itoh, M.; Suganami, T.; Satoh, N.; Tanimoto-Koyama, K.; Yuan, X.; Tanaka, M.; Kawano, H.; Yano, T.; Aoe, S.; Takeya, M.; Shimatsu, A.; Kuzuya, H.; Kamei, Y.; Ogawa, Y., Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arteriosclerosis, thrombosis, and vascular biology, 2007, 27, 1918-1925.
161. Neschen, S.; Morino, K.; Rossbacher, J.C.; Pongratz, R.L.; Cline, G.W.; Sono, S.; Gillum, M.; Shulman, G.I., Fish Oil Regulates Adiponectin Secretion by a Peroxisome Proliferator-Activated Receptor{gamma}-Dependent Mechanism in Mice. Diabetes, 2006, 55, 924-928.
162. Guebre-Egziabher, F.; Rabasa-Lhoret, R.; Bonnet, F.; Bastard, J.P.; Desage, M.; Skilton, M.R.; Vidal, H.; Laville, M., Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. European journal of clinical nutrition, 2008, 62, 1287-1293.
163. Stryjecki, C.; Mutch, D.M., Fatty acid-gene interactions, adipokines and obesity. European journal of clinical nutrition, 2011, 65, 285-297.
164. Yokoyama, M.; Origasa, H.; Matsuzaki, M.; Matsuzawa, Y.; Saito, Y.; Ishikawa, Y.; Oikawa, S.; Sasaki, J.; Hishida, H.; Itakura, H.; Kita, T.; Kitabatake, A.; Nakaya, N.; Sakata, T.; Shimada, K.; Shirato, K., Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Int J Environ Res Public Health, 2007, 369, 1090-1098.
165. Kondo, K.; Morino, K.; Nishio, Y.; Kondo, M.; Fuke, T.; Ugi, S.; Iwakawa, H.; Kashiwagi, A.; Maegawa, H., Effects of a fish-based diet on the serum adiponectin concentration in young, non-obese, healthy Japanese subjects. Journal of atherosclerosis and thrombosis, 2010, 17, 628-637.
166. Krebs, J.D.; Browning, L.M.; McLean, N.K.; Rothwell, J.L.; Mishra, G.D.; Moore, C.S.; Jebb, S.A., Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women. International journal of obesity, 2006, 30, 1535-1544.
167. Syvertsen, C.; Halse, J.; Hoivik, H.O.; Gaullier, J.M.; Nurminiemi, M.; Kristiansen, K.; Einerhand, A.; O'Shea, M.; Gudmundsen, O., The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese. International journal of obesity, 2007, 31, 1148-1154.
168. Chachay, V.S.; Kirkpatrick, C.M.; Hickman, I.J.; Ferguson, M.; Prins, J.B.; Martin, J.H., Resveratrol-pills to replace a healthy diet? Br J Clin Pharmacol, 2011, 72, 27-38.
169. Micallef, M.A.; Garg, M.L., Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals. Atherosclerosis, 2009, 204, 476-482.
170. Perelas, A.; Tsoulkani, A.; Perrea, D., Effects of lipid-lowering drugs on adiponectin. Curr Vasc Pharmacol, 2010, 8, 836-848.
171. Timmers, S.; Konings, E.; Bilet, L.; Houtkooper, R.H.; van de Weijer, T.; Goossens, G.H.; Hoeks, J.; van der Krieken, S.; Ryu, D.; Kersten, S.; Moonen-Kornips, E.; Hesselink, M.K.; Kunz, I.; SchrauwenHinderling, V.B.; Blaak, E.E.; Auwerx, J.; Schrauwen, P., Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab, 2011, 14, 612-622.
172. Crandall, J.P.; Oram, V.; Trandafirescu, G.; Reid, M.; Kishore, P.; Hawkins, M.; Cohen, H.W.; Barzilai, N., Pilot Study of Resveratrol in Older Adults With Impaired Glucose Tolerance. J Gerontol A Biol Sci Med Sci, 2012.
173. Kadooka, Y.; Sato, M.; Imaizumi, K.; Ogawa, A.; Ikuyama, K.; Akai, Y.; Okano, M.; Kagoshima, M.; Tsuchida, T., Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. European journal of clinical nutrition, 2010, 64, (6), 636-643.
174. Newburg, D.S.; Woo, J.G.; Morrow, A.L., Characteristics and potential functions of human milk adiponectin. J Pediatr, 2010, 156, S41-46.
175. Luoto, R.; Laitinen, K.; Nermes, M.; Isolauri, E., Impact of maternal probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration: A prospective, randomized, placebocontrolled study. Early Hum Dev, 2012, 88, 339-344
176. Mencarelli, A.; Distrutti, E.; Renga, B.; D'Amore, C.; Cipriani, S.; Palladino, G.; Donini, A.; Ricci, P.; Fiorucci, S., Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation. PLoS One, 2011, 6, e22978.
177. Imbeault, P.; Pomerleau, M.; Harper, M.E.; Doucet, E., Unchanged fasting and postprandial adiponectin levels following a 4-day caloric restriction in young healthy men. Clin Endocrinol (Oxf), 2004, 60, 429-433.
178. Gavrila, A.; Chan, J.L.; Yiannakouris, N.; Kontogianni, M.; Miller, L.C.; Orlova, C.; Mantzoros, C.S., 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. The Journal of clinical endocrinology and metabolism, 2003, 88, 4823-4831.
179. Merl, V.; Peters, A.; Oltmanns, K.M.; Kern, W.; Born, J.; Fehm, H.L.; Schultes, B., Serum adiponectin concentrations during a 72-hour fast in overand normal-weight humans. International journal of obesity, 2005, 29, 998-1001.
180. Klempel, M.C.; Varady, K.A., Reliability of leptin, but not adiponectin, as a biomarker for diet-induced weight loss in humans. Nutrition reviews, 2011, 69, (3), 145-154.
181. Sigal, R.J.; Kenny, G.P.; Wasserman, D.H.; Castaneda-Sceppa, C.; White, R.D., Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes care, 2006, 29, 1433-1438.
182. Tresierras, M.A.; Balady, G.J., Resistance training in the treatment of diabetes and obesity: mechanisms and outcomes. J Cardiopulm Rehabil Prev, 2009, 29, 67-75.
183. Hills, A.P.; Shultz, S.P.; Soares, M.J.; Byrne, N.M.; Hunter, G.R.; King, N.A.; Misra, A., Resistance training for obese, type 2 diabetic adults: a review of the evidence. Obesity reviews : an official journal of the International Association for the Study of Obesity, 2010, 11, 740-749.
184. Simpson, K.A.; Singh, M.A., Effects of exercise on adiponectin: a systematic review. Obesity (Silver Spring), 2008, 16, 241-256.
185. Hara, T.; Fujiwara, H.; Nakao, H.; Mimura, T.; Yoshikawa, T.; Fujimoto, S., Body composition is related to increase in plasma adiponectin levels rather than training in young obese men. European journal of applied physiology, 2005, 94, 520-526.
186. Klimcakova, E.; Polak, J.; Moro, C.; Hejnova, J.; Majercik, M.; Viguerie, N.; Berlan, M.; Langin, D.; Stich, V., Dynamic strength training improves insulin sensitivity without altering plasma levels and gene expression of adipokines in subcutaneous adipose tissue in obese men. The Journal of clinical endocrinology and metabolism, 2006, 91, 5107-5112.
187. Moghadasi, M.; Mohebbi, H.; Rahmani-Nia, F.; Hassan-Nia, S.; Noroozi, H.; Pirooznia, N., Highintensity endurance training improves adiponectin mRNA and plasma concentrations. Eur J Appl Physiol, 2011.
188. Fatouros, I.G.; Tournis, S.; Leontsini, D.; Jamurtas, A.Z.; Sxina, M.; Thomakos, P.; Manousaki, M.; Douroudos, I.; Taxildaris, K.; Mitrakou, A., Leptin and adiponectin responses in overweight inactive elderly following resistance training and detraining are intensity related. J Clin Endocrinol Metab, 2005, 90, 5970-5977.
189. O'Leary, V.B.; Jorett, A.E.; Marchetti, C.M.; Gonzalez, F.; Phillips, S.A.; Ciaraldi, T.P.; Kirwan, J.P., Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin-resistant adults. American journal of physiology. Endocrinology and metabolism, 2007, 293, E421-427.
190. Christiansen, T.; Paulsen, S.K.; Bruun, J.M.; Ploug, T.; Pedersen, S.B.; Richelsen, B., Diet-Induced Weight Loss and Exercise Alone and in Combination Enhance the Expression of Adiponectin Receptors in Adipose Tissue and Skeletal Muscle, but Only Diet-Induced Weight Loss Enhanced Circulating Adiponectin. J Clin Endocrinol Metab, 2010, 95, 911-919.
191. Kelly, K.R.; Blaszczak, A.; Haus, J.M.; Patrick-Melin, A.; Fealy, C.E.; Solomon, T.P.; Kalinski, M.I.; Kirwan, J.P., A 7-Day Exercise Program Increases High Molecular Weight Adiponectin in Obese Adults. Med Sci Sports Exerc, 2011.
192. Rodríguez, A.; Catalán, V.; Becerril, S.; Gil, M.J.; Mugueta, C.; Gómez-Ambrosi, J.; Fruhbeck, G., Impaired adiponectin-AMPK signalling in insulin-sensitive tissues of hypertensive rats. Life Sciences, 2008, 83, 540-549.
193. Vu, V.; Riddell, M.C.; Sweeney, G., Circulating adiponectin and adiponectin receptor expression in skeletal muscle: effects of exercise. Diabetes Metab Res Rev, 2007, 23, 600-611.
194. Shetty, S.; Kusminski, C.M.; Scherer, P.E., Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies. Trends Pharmacol Sci, 2009, 30, 234-239.
195. Arsenescu, V.; Narasimhan, M.L.; Halide, T.; Bressan, R.A.; Barisione, C.; Cohen, D.A.; de Villiers, W.J.; Arsenescu, R., Adiponectin and plant-derived Mammalian adiponectin homolog exert a protective effect in murine colitis. Dig Dis Sci, 2011, 56, 2818-2832.
196. Otvos, L., Jr.; Haspinger, E.; Larussa, F.; Maspero, F.; Graziano, P.; Kovalszky, I.; Lovas, S.; Nama, K.; Hoffmann, R.; Knappe, D.; Cassone, M.; Wade, J.; Surmacz, E., Design and Development of a Peptidebased Adiponectin Receptor Agonist for Cancer Treatment. BMC Biotechnol, 2011, 11, 90.
197. Goldfine, A.B.; Fonseca, V.; Jablonski, K.A.; Pyle, L.; Staten, M.A.; Shoelson, S.E., The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med, 2010, 152, 346-357.
198. Goldfine, A.B.; Silver, R.; Aldhahi, W.; Cai, D.; Tatro, E.; Lee, J.; Shoelson, S.E., Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci, 2008, 1, 36-43.