Table of Contents Author Guidelines Submit a Manuscript
Journal of Obesity
Volume 2011, Article ID 168659, 17 pages
http://dx.doi.org/10.1155/2011/168659
Review Article

Variations in Adipokine Genes AdipoQ, Lep, and LepR Are Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

1Department of Physiology, University of Manitoba and Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Tache Ave, Winnipeg, Manitoba, Canada R2H 2A6
2Departments of Human Nutritional Sciences and Physiology, University of Manitoba, 351 Tache Ave, Winnipeg, Manitoba, Canada R2H 2A6
3Departments of Physiology and Human Nutritional Sciences, University of Manitoba and Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Tache Ave, Winnipeg, Manitoba, Canada R2H 2A6

Received 9 January 2011; Accepted 10 March 2011

Academic Editor: P. Trayhurn

Copyright © 2011 Jennifer Emily Enns et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. B. Schelbert, “Comorbidities of Obesity,” Primary Care, vol. 36, no. 2, pp. 271–285, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. E. E. Calle, C. Rodriguez, K. Walker-Thurmond, and M. J. Thun, “Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults,” New England Journal of Medicine, vol. 348, no. 17, pp. 1625–1638, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. C. Samanic, W. H. Chow, G. Gridley, B. Jarvholm, and J. F. Fraumeni Jr., “Relation of body mass index to cancer risk in 362,552 Swedish men,” Cancer Causes and Control, vol. 17, no. 7, pp. 901–909, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. O. Ukkola and C. Bouchard, “Clustering of metabolic abnormalities in obese individuals: the role of genetic factors,” Annals of Medicine, vol. 33, no. 2, pp. 79–90, 2001. View at Google Scholar · View at Scopus
  5. K. M. Flegal, M. D. Carroll, C. L. Ogden, and L. R. Curtin, “Prevalence and trends in obesity among US adults, 1999–2008,” Journal of the American Medical Association, vol. 303, no. 3, pp. 235–241, 2010. View at Publisher · View at Google Scholar
  6. P. G. Kopelman, “Obesity as a medical problem,” Nature, vol. 404, no. 6778, pp. 635–643, 2000. View at Google Scholar · View at Scopus
  7. P. Trayhurn and I. S. Wood, “Adipokines: inflammation and the pleiotropic role of white adipose tissue,” British Journal of Nutrition, vol. 92, no. 3, pp. 347–355, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. F. Y. Li, K. K. Cheng, K. S. Lam, P. M. Vanhoutte, and A. Xu, “Cross-talk between adipose tissue and vasculature: role of adiponectin,” Acta Physiologica. In press.
  9. H. Hauner, “Secretory factors from human adipose tissue and their functional role,” Proceedings of the Nutrition Society, vol. 64, no. 2, pp. 163–169, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Bluher, “Adipose tissue dysfunction in obesity,” Experimental and Clinical Endocrinology and Diabetes, vol. 117, no. 6, pp. 241–250, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. H. E. Bays, J. M. González-Campoy, G. A. Bray et al., “Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity,” Expert Review of Cardiovascular Therapy, vol. 6, no. 3, pp. 343–368, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Yamauchi, J. Kamon, H. Waki et al., “The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity,” Nature Medicine, vol. 7, no. 8, pp. 941–946, 2001. View at Publisher · View at Google Scholar · View at Scopus
  13. T. Yamauchi, J. Kamon, Y. Minokoshi et al., “Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase,” Nature Medicine, vol. 8, no. 11, pp. 1288–1295, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. T. Kadowaki and T. Yamauchi, “Adiponectin and adiponectin receptors,” Endocrine Reviews, vol. 26, no. 3, pp. 439–451, 2005. View at Publisher · View at Google Scholar
  15. J. J. Díez and P. Iglesias, “The role of the novel adipocyte-derived hormone adiponectin in human disease,” European Journal of Endocrinology, vol. 148, no. 3, pp. 293–300, 2003. View at Publisher · View at Google Scholar
  16. K. Hotta, T. Funahashi, Y. Arita et al., “Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 6, pp. 1595–1599, 2000. View at Google Scholar · View at Scopus
  17. P. Trayhurn and I. S. Wood, “Signalling role of adipose tissue: adipokines and inflammation in obesity,” Biochemical Society Transactions, vol. 33, no. 5, pp. 1078–1081, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. G. R. Hajer, T. W. Van Haeften, and F. L. J. Visseren, “Adipose tissue dysfunction in obesity, diabetes, and vascular diseases,” European Heart Journal, vol. 29, no. 24, pp. 2959–2971, 2008. View at Publisher · View at Google Scholar
  19. E. Maury and S. M. Brichard, “Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome,” Molecular and Cellular Endocrinology, vol. 314, no. 1, pp. 1–16, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Matsuzawa, “Adiponectin: a key player in obesity related disorders,” Current Pharmaceutical Design, vol. 16, no. 17, pp. 1896–1901, 2010. View at Publisher · View at Google Scholar
  21. N. Vionnet, E. H. Hani, S. Dupont et al., “Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosiome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24,” American Journal of Human Genetics, vol. 67, no. 6, pp. 1470–1480, 2000. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Francke, M. Manraj, C. Lacquemant et al., “A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27,” Human Molecular Genetics, vol. 10, no. 24, pp. 2751–2765, 2001. View at Google Scholar · View at Scopus
  23. F. Vasseur, N. Helbecque, C. Dina et al., “Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians,” Human Molecular Genetics, vol. 11, no. 21, pp. 2607–2614, 2002. View at Google Scholar · View at Scopus
  24. B. V. De Courten, R. L. Hanson, T. Funahashi et al., “Common polymorphisms in the adiponectin gene ACDC are not associated with diabetes in Pima Indians,” Diabetes, vol. 54, no. 1, pp. 284–289, 2005. View at Publisher · View at Google Scholar
  25. L. M. Chuang, Y. F. Chiu, W. H. H. Sheu et al., “Biethnic comparisons of autosomal genomic scan for loci linked to plasma adiponectin in populations of chinese and Japanese origin,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 11, pp. 5772–5778, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. A. G. Comuzzie, T. Funahashi, G. Sonnenberg et al., “The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 9, pp. 4321–4325, 2001. View at Publisher · View at Google Scholar · View at Scopus
  27. X. Guo, M. F. Saad, C. D. Langefeld et al., “Genome-wide linkage of plasma adiponectin reveals a major locus on chromosome 3q distinct from the adiponectin structural gene: the IRAS Family Study,” Diabetes, vol. 55, no. 6, pp. 1723–1730, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. R. S. Lindsay, T. Funahashi, J. Krakoff et al., “Genome-wide linkage analysis of serum adiponectin in the Pima Indian population,” Diabetes, vol. 52, no. 9, pp. 2419–2425, 2003. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Menzaghi, V. Trischitta, and A. Doria, “Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease,” Diabetes, vol. 56, no. 5, pp. 1198–1209, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. H. F. Gu, “Biomarkers of adiponectin: plasma protein variation and genomic DNA polymorphisms,” Biomarker Insights, vol. 4, pp. 123–133, 2009. View at Google Scholar
  31. N. Bouatia-Naji, D. Meyre, S. Lobbens et al., “ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity,” Diabetes, vol. 55, no. 2, pp. 545–550, 2006. View at Publisher · View at Google Scholar
  32. C. Menzaghi, T. Ercolino, L. Salvemini et al., “Multigenic control of serum adiponectin levels: evidence for a role of the APM1 gene and a locus on 14q13,” Physiological Genomics, vol. 19, pp. 170–174, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. A. Morandi, C. Maffeis, S. Lobbens et al., “Early detrimental metabolic outcomes of rs17300539-A Allele of ADIPOQ gene despite higher adiponectinemia,” Obesity, vol. 18, no. 7, pp. 1469–1473, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. F. Fumeron, R. Aubert, A. Siddiq et al., “Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study,” Diabetes, vol. 53, no. 4, pp. 1150–1157, 2004. View at Publisher · View at Google Scholar
  35. M. Yang, C. C. Qui, W. Chen, L. L. Xu, M. Yu, and H. D. Xiang, “Identification of a regulatory single nucleotide polymorphism in the adiponectin (APM1) gene associated with type 2 diabetes in Han nationality,” Biomedical and Environmental Sciences, vol. 21, no. 6, pp. 454–459, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. H. F. Gu, A. Abulaiti, C.-G. Östenson et al., “Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish Caucasians,” Diabetes, vol. 53, supplement 1, pp. S31–S35, 2004. View at Google Scholar
  37. F. Gibson and P. Froguel, “Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility in French Caucasians,” Diabetes, vol. 53, no. 11, pp. 2977–2983, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. P. Henneman, Y. S. Aulchenko, R. R. Frants et al., “Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits,” Diabetes Care, vol. 33, no. 4, pp. 908–913, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. T. Kyriakou, L. J. Collins, N. J. Spencer-Jones et al., “Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity,” Journal of Human Genetics, vol. 53, no. 8, pp. 718–727, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. J. G. Woo, L. M. Dolan, R. Deka et al., “Interactions between noncontiguous haplotypes in the adiponectin gene ACDC are associated with plasma adiponectin,” Diabetes, vol. 55, no. 2, pp. 523–529, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. M. F. Hivert, A. K. Manning, J. B. McAteer et al., “Common variants in the adiponectin gene (ADIPOQ) associated with plasma adiponectin levels, type 2 diabetes, and diabetes-related quantitative traits: the framingham offspring study,” Diabetes, vol. 57, no. 12, pp. 3353–3359, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. F. Vasseur, N. Helbecque, S. Lobbens et al., “Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity,” Diabetologia, vol. 48, no. 5, pp. 892–899, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. K. L. Ong, M. Li, A. W. K. Tso et al., “Association of genetic variants in the adiponectin gene with adiponectin level and hypertension in Hong Kong Chinese,” European Journal of Endocrinology, vol. 163, no. 2, pp. 251–257, 2010. View at Publisher · View at Google Scholar
  44. S. L. Prior, D. R. Gable, J. A. Cooper et al., “Association between the adiponectin promoter rs266729 gene variant and oxidative stress in patients with diabetes mellitus,” European Heart Journal, vol. 30, no. 10, pp. 1263–1269, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. G. Hoefle, A. Muendlein, C. H. Saely et al., “The -11377 C>G promoter variant of the adiponectin gene, prevalence of coronary atherosclerosis, and incidence of vascular events in men,” Thrombosis and Haemostasis, vol. 97, no. 3, pp. 451–457, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Pechlivanis, J. L. Bermejo, B. Pardini et al., “Genetic variation in adipokine genes and risk of colorectal cancer,” European Journal of Endocrinology, vol. 160, no. 6, pp. 933–940, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. L. G. Carvajal-Carmona, S. Spain, D. Kerr, R. Houlston, J. B. Cazier, and I. Tomlinson, “Common variation at the adiponectin locus is not associated with colorectal cancer risk in the UK,” Human Molecular Genetics, vol. 18, no. 10, pp. 1889–1892, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. V. G. Kaklamani, K. B. Wisinski, M. Sadim et al., “Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk,” Journal of the American Medical Association, vol. 300, no. 13, pp. 1523–1531, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. LU. Qi, A. Doria, J. E. Manson et al., “Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in patients with type 2 diabetes,” Diabetes, vol. 55, no. 5, pp. 1512–1516, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. C. L. Wassel, J. S. Pankow, D. R. Jacobs Jr., M. W. Steffes, NA. Li, and P. J. Schreiner, “Variants in the Adiponectin Gene and Serum Adiponectin: The Coronary Artery Development in Young Adults (CARDIA) Study,” Obesity, vol. 18, no. 12, pp. 2333–2338, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. S.-M. Ruchat, R. J. F. Loos, T. Rankinen et al., “Associations between glucose tolerance, insulin sensitivity and insulin secretion phenotypes and polymorphisms in adiponectin and adiponectin receptor genes in the Quebec Family Study,” Diabetic Medicine, vol. 25, no. 4, pp. 400–406, 2008. View at Publisher · View at Google Scholar
  52. G. Mohammadzadeh and N. Zarghami, “Associations between single-nucleotide polymorphisms of the adiponectin gene, serum adiponectin levels and increased risk of type 2 diabetes mellitus in Iranian obese individuals,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 69, no. 7, pp. 764–771, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. C. F. Low, E. R. Mohd Tohit, P. P. Chong, and F. Idris, “Adiponectin SNP45TG is associated with gestational diabetes mellitus,” Archives of Gynecology and Obstetrics. In press. View at Publisher · View at Google Scholar · View at Scopus
  54. L. Melistas, C. S. Mantzoros, M. Kontogianni, S. Antonopoulou, J. M. Ordovas, and N. Yiannakouris, “Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women,” European Journal of Endocrinology, vol. 161, no. 6, pp. 845–852, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. Z. L. Wang, B. Xia, U. Shrestha et al., “Correlation between adiponectin polymorphisms and non-alcoholic fatty liver disease with or without metabolic syndrome in Chinese population,” Journal of Endocrinological Investigation, vol. 31, no. 12, pp. 1086–1091, 2008. View at Google Scholar · View at Scopus
  56. K. Hara, P. Boutin, Y. Mori et al., “Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population,” Diabetes, vol. 51, no. 2, pp. 536–540, 2002. View at Google Scholar · View at Scopus
  57. L. L. Li, X. L. Kang, X. J. Ran et al., “Associations between 45T/G polymorphism of the adiponectin gene and plasma adiponectin levels with type 2 diabetes,” Clinical and Experimental Pharmacology and Physiology, vol. 34, no. 12, pp. 1287–1290, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. B. S. Sutton, S. Weinert, C. D. Langefeld et al., “Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family Study,” Human Genetics, vol. 117, no. 2-3, pp. 107–118, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Y. Lee, N. S. Lee, Y. M. Cho et al., “Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population,” Diabetic Medicine, vol. 22, no. 5, pp. 569–575, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. V. Mackevics, I. M. Heid, S. A. Wagner et al., “The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians,” European Journal of Human Genetics, vol. 14, no. 3, pp. 349–356, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. J. L. González-Sánchez, C. A. Zabena, M. T. Martínez-Larrad et al., “An SNP in the adiponectin gene is associated with decreased serum adiponectin levels and risk for impaired glucose tolerance,” Obesity Research, vol. 13, no. 5, pp. 807–812, 2005. View at Google Scholar · View at Scopus
  62. J. Zacharova, J. -L. Chiasson, and M. Laakso, “The common polymorphisms (Single Nucleotide Polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial,” Diabetes, vol. 54, no. 3, pp. 893–899, 2005. View at Publisher · View at Google Scholar
  63. K. Nakatani, K. Noma, J. Nishioka et al., “Adiponectin gene variation associates with the increasing risk of type 2 diabetes in non-diabetic Japanese subjects,” International Journal of Molecular Medicine, vol. 15, no. 1, pp. 173–177, 2005. View at Google Scholar · View at Scopus
  64. O. Ukkola, E. Ravussin, P. Jacobson, L. Sjöström, and C. Bouchard, “Mutations in the adiponectin gene in lean and obese subjects from the Swedish obese subjects cohort,” Metabolism: Clinical and Experimental, vol. 52, no. 7, pp. 881–884, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Bacci, C. Menzaghi, T. Ercolino et al., “The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients,” Diabetes Care, vol. 27, no. 8, pp. 2015–2020, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. C. Lacquemant, P. Froguel, S. Lobbens, P. Izzo, C. Dina, and J. Ruiz, “The adiponectin gene SNP+45 is associated with coronary artery disease in Type 2 (non-insulin-dependent) diabetes mellitus,” Diabetic Medicine, vol. 21, no. 7, pp. 776–781, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. J. L. Beebe-Dimmer, K. A. Zuhlke, A. M. Ray, E. M. Lange, and K. A. Cooney, “Genetic variation in adiponectin (ADIPOQ) and the type 1 receptor (ADIPOR1), obesity and prostate cancer in African Americans,” Prostate Cancer and Prostatic Diseases, vol. 13, no. 4, pp. 362–368, 2010. View at Publisher · View at Google Scholar
  68. MC Huang, TN Wang, KT Lee et al., “Adiponectin gene SNP276 variants and central obesity confer risks for hyperglycemia in indigenous Taiwanese,” The Kaohsiung Journal of Medical Sciences, vol. 26, pp. 227–236, 2010. View at Google Scholar
  69. F. Mousavinasab, T. Tähtinen, J. Jokelainen et al., “Common polymorphisms (single-nucleotide polymorphisms SNP+45 and SNP+276) of the adiponectin gene regulate serum adiponectin concentrations and blood pressure in young Finnish men,” Molecular Genetics and Metabolism, vol. 87, no. 2, pp. 147–151, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. E. Verduci, S. Scaglioni, C. Agostoni et al., “The relationship of insulin resistance with SNP 276G>T at adiponectin gene and plasma long-chain polyunsaturated fatty acids in obese children,” Pediatric Research, vol. 66, no. 3, pp. 346–349, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. LU. Qi, T. Li, E. Rimm et al., “The +276 polymorphism of the APM1 gene, plasma adiponectin concentration, and cardiovascular risk in diabetic men,” Diabetes, vol. 54, no. 5, pp. 1607–1610, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. E. Filippi, F. Sentinelli, S. Romeo et al., “The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age ≤50 years),” Journal of Molecular Medicine, vol. 83, no. 9, pp. 711–719, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Jang, J. H. Lee, J. S. Chae et al., “Association of the 276G→T polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans,” American Journal of Clinical Nutrition, vol. 82, no. 4, pp. 760–767, 2005. View at Google Scholar · View at Scopus
  74. Y. Iwashima, T. Katsuya, K. Ishikawa et al., “Hypoadiponectinemia is an independent risk factor for hypertension,” Hypertension, vol. 43, no. 6, pp. 1318–1323, 2004. View at Publisher · View at Google Scholar · View at Scopus
  75. K. S. Vimaleswaran, V. Radha, K. Ramya et al., “A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians,” Human Genetics, vol. 123, no. 6, pp. 599–605, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. C. Specchia, K. Scott, P. Fortina, M. Devoto, and B. Falkner, “Association of a polymorphic variant of the adiponectin gene with Insulin resistance in African Americans,” Clinical and Translational Science, vol. 1, no. 3, pp. 194–199, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. J. F. Ferguson, C. M. Phillips, A. C. Tierney et al., “Gene-nutrient interactions in the metabolic syndrome: single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance,” American Journal of Clinical Nutrition, vol. 91, no. 3, pp. 794–801, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. D. Zhang, J. Ma, K. Brismar, S. Efendic, and H. F. Gu, “A single nucleotide polymorphism alters the sequence of SP1 binding site in the adiponectin promoter region and is associated with diabetic nephropathy among type 1 diabetic patients in the Genetics of Kidneys in Diabetes Study,” Journal of Diabetes and its Complications, vol. 23, no. 4, pp. 265–272, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. H. Laumen, A. D. Saningong, I. M. Heid et al., “Functional characterization of promoter variants of the adiponectin gene complemented by epidemiological data,” Diabetes, vol. 58, no. 4, pp. 984–991, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. W. S. Yang, P. L. Tsou, W. J. Lee et al., “Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity,” Journal of Molecular Medicine, vol. 81, no. 7, pp. 428–434, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. C. Menzaghi, T. Ercolino, R. D. Paola et al., “A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome,” Diabetes, vol. 51, no. 7, pp. 2306–2312, 2002. View at Google Scholar · View at Scopus
  82. F. Abbasi, J. W. Chu, C. Lamendola et al., “Discrimination between obesity and insulin resistance in the relationship with adiponectin,” Diabetes, vol. 53, no. 3, pp. 585–590, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. P. Pérez-Martínez, J. López-Miranda, C. Cruz-Teno et al., “Adiponectin gene variants are associated with insulin sensitivity in response to dietary fat consumption in caucasian men,” Journal of Nutrition, vol. 138, no. 9, pp. 1609–1614, 2008. View at Google Scholar · View at Scopus
  84. D. Warodomwichit, J. Shen, D. K. Arnett et al., “ADIPOQ polymorphisms, monounsaturated fatty acids, and obesity risk: the GOLDN study,” Obesity, vol. 17, no. 3, pp. 511–517, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. H. K. Chung, J. S. Chae, Y. Hyun et al., “Influence of adiponectin gene polymorphisms on adiponectin level and insulin resistance index in response to dietary intervention in overweight-obese patients with impaired fasting glucose or newly diagnosed type 2 diabetes,” Diabetes Care, vol. 32, no. 4, pp. 552–558, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. K. Tsuzaki, K. Kotani, N. Nagai et al., “Adiponectin gene single-nucleotide polymorphisms and treatment response to obesity,” Journal of Endocrinological Investigation, vol. 32, no. 5, pp. 395–400, 2009. View at Google Scholar · View at Scopus
  87. T. Skurk, C. Alberti-Huber, C. Herder, and H. Hauner, “Relationship between adipocyte size and adipokine expression and secretion,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 3, pp. 1023–1033, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. G. Fantuzzi, “Adipose tissue, adipokines, and inflammation,” Journal of Allergy and Clinical Immunology, vol. 115, no. 5, pp. 911–920, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. P. J. Scarpace and Y. Zhang, “Elevated leptin: consequence or cause of obesity?” Frontiers in Bioscience, vol. 12, pp. 3531–3544, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. T. A. Dardeno, S. H. Chou, H. S. Moon, J. P. Chamberland, C. G. Fiorenza, and C. S. Mantzoros, “Leptin in human physiology and therapeutics,” Frontiers in Neuroendocrinology, vol. 31, no. 3, pp. 377–393, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. A. Stofkova, “Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity,” Endocrine Regulations, vol. 43, no. 4, pp. 157–168, 2009. View at Google Scholar · View at Scopus
  92. J. P. Thaler and M. W. Schwartz, “Minireview: inflammation and obesity pathogenesis: the hypothalamus heats up,” Endocrinology, vol. 151, no. 9, pp. 4109–4115, 2010. View at Publisher · View at Google Scholar
  93. D. L. Coleman, “Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice,” Diabetologia, vol. 14, no. 3, pp. 141–148, 1978. View at Google Scholar · View at Scopus
  94. S. A. Ranadive and C. Vaisse, “Lessons from extreme human obesity: monogenic disorders,” Endocrinology and Metabolism Clinics of North America, vol. 37, no. 3, pp. 733–751, 2008. View at Publisher · View at Google Scholar · View at Scopus
  95. Y. Friedlander, G. Li, M. Fornage et al., “Candidate molecular pathway genes related to appetite regulatory neural network, adipocyte homeostasis and obesity: results from the CARDIA Study,” Annals of Human Genetics, vol. 74, no. 5, pp. 387–398, 2010. View at Publisher · View at Google Scholar
  96. N. Y. Souren, A. D. Paulussen, A. Steyls et al., “Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins,” International Journal of Obesity, vol. 32, no. 8, pp. 1233–1239, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. A. Meirhaeghe, D. Cottel, P. Amouyel, and J. Dallongeville, “Lack of association between certain candidate gene polymorphisms and the metabolic syndrome,” Molecular Genetics and Metabolism, vol. 86, no. 1-2, pp. 293–299, 2005. View at Publisher · View at Google Scholar · View at Scopus
  98. R. Lucantoni, E. Ponti, M. E. Berselli et al., “The A19G polymorphism in the 5' untranslated region of the human obese gene does not affect leptin levels in severely obese patients,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 10, pp. 3589–3591, 2000. View at Google Scholar · View at Scopus
  99. J. Hager, K. Clement, S. Francke et al., “A polymorphism in the 5' untranslated region of the human ob gene is associated with low leptin levels,” International Journal of Obesity, vol. 22, no. 3, pp. 200–205, 1998. View at Google Scholar
  100. M. L. Hart Sailors, A. R. Folsom, C. M. Ballantyne et al., “Genetic variation and decreased risk for obesity in the Atherosclerosis Risk in Communities Study,” Diabetes, Obesity and Metabolism, vol. 9, no. 4, pp. 548–557, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. Y. Jiang, J. B. Wilk, I. Borecki et al., “Common variants in the 5′ region of the leptin gene are associated with body mass index in men from the National Heart, Lung, and Blood Institute Family Heart Study,” American Journal of Human Genetics, vol. 75, no. 2, pp. 220–230, 2004. View at Publisher · View at Google Scholar · View at Scopus
  102. O. Mammès, D. Betoulle, R. Aubert, B. Herbeth, G. Siest, and F. Fumeron, “Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight,” Annals of Human Genetics, vol. 64, no. 5, pp. 391–394, 2000. View at Publisher · View at Google Scholar · View at Scopus
  103. O. Portolés, J. V. Sorlí, F. Francés et al., “Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain,” European Journal of Epidemiology, vol. 21, no. 8, pp. 605–612, 2006. View at Publisher · View at Google Scholar
  104. D. Murugesan, T. Arunachalam, V. Ramamurthy, and S. Subramanian, “Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore,” Indian Journal of Human Genetics, vol. 16, pp. 72–77, 2010. View at Google Scholar
  105. N. D. Quinton, A. J. Lee, R. J. M. Ross, R. Eastell, and A. I. F. Blakemore, “A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women,” Human Genetics, vol. 108, no. 3, pp. 233–236, 2001. View at Publisher · View at Google Scholar · View at Scopus
  106. V. S. Mattevi, V. M. Zembrzuski, and M. H. Hutz, “Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil,” International Journal of Obesity, vol. 26, no. 9, pp. 1179–1185, 2002. View at Publisher · View at Google Scholar
  107. N. Yiannakouris, M. Yannakoulia, L. Melistas, J. L. Chan, D. Klimis-Zacas, and C. S. Mantzoros, “The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 9, pp. 4434–4439, 2001. View at Publisher · View at Google Scholar · View at Scopus
  108. N. Stefan, B. Vozarova, A. Del Parigi et al., “The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism,” International Journal of Obesity, vol. 26, no. 12, pp. 1629–1632, 2002. View at Publisher · View at Google Scholar
  109. K. C. Chiu, A. Chu, L. M. Chuang, and M. F. Saad, “Association of leptin receptor polymorphism with insulin resistance,” European Journal of Endocrinology, vol. 150, no. 5, pp. 725–729, 2004. View at Publisher · View at Google Scholar · View at Scopus
  110. G. M. Van Der Vleuten, L. A. Kluijtmans, A. Hijmans, H. J. Blom, A. F. H. Stalenhoef, and J. De Graaf, “The Gln223Arg polymorphism in the leptin receptor is associated with familial combined hyperlipidemia,” International Journal of Obesity, vol. 30, no. 6, pp. 892–898, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. S. F. Pimentel Duarte, E. A. Francischetti, V. Genelhu-Abreu et al., “p.Q223R leptin receptor polymorphism associated with obesity in Brazilian multiethnic subjects,” American Journal of Human Biology, vol. 18, no. 4, pp. 448–453, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. M. Wauters, I. Mertens, M. Chagnon et al., “Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women,” International Journal of Obesity, vol. 25, no. 5, pp. 714–720, 2001. View at Publisher · View at Google Scholar
  113. T. Ogawa, H. Hirose, Y. Yamamoto et al., “Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population,” Metabolism, vol. 53, no. 7, pp. 879–885, 2004. View at Publisher · View at Google Scholar
  114. U. L. Fairbrother, L. B. Tankó, A. J. Walley, C. Christiansen, P. Froguel, and A. I. F. Blakemore, “Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women,” Journal of Bone and Mineral Research, vol. 22, no. 4, pp. 544–550, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Rosmond, Y. C. Chagnon, G. Holm et al., “Hypertension in obesity and the leptin receptor gene locus,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 9, pp. 3126–3131, 2000. View at Google Scholar · View at Scopus
  116. Y. C. Chagnon, W. K. Chung, L. Pérusse, M. Chagnon, R. L. Leibel, and C. Bouchard, “Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Quebec Family Study,” International Journal of Obesity, vol. 23, no. 3, pp. 278–286, 1999. View at Google Scholar
  117. J. M. Guízar-Mendoza, N. Amador-Licona, S. E. Flores-Martínez, M. G. López-Cardona, R. Ahuatzin-Trémary, and J. Sánchez-Corona, “Association analysis of the Gln223Arg polymorphism in the human leptin receptor gene, and traits related to obesity in Mexican adolescents,” Journal of Human Hypertension, vol. 19, no. 5, pp. 341–346, 2005. View at Publisher · View at Google Scholar · View at Scopus
  118. T. Salopuro, L. Pulkkinen, J. Lindström et al., “Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: the Finnish Diabetes Prevention Study,” International Journal of Obesity, vol. 29, no. 10, pp. 1245–1251, 2005. View at Publisher · View at Google Scholar · View at Scopus
  119. L. Gallicchio, H. H. Chang, D. K. Christo et al., “Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study,” BMC Medical Genetics, vol. 10, article no. 103, 2009. View at Publisher · View at Google Scholar · View at Scopus
  120. O. Mammès, R. Aubert, D. Betoulle et al., “LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women,” European Journal of Clinical Investigation, vol. 31, no. 5, pp. 398–404, 2001. View at Publisher · View at Google Scholar · View at Scopus
  121. Y. J. Liu, S. M. S. Rocha-Sanchez, P. Y. Liu et al., “Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families,” Physiological Genomics, vol. 17, pp. 101–106, 2004. View at Publisher · View at Google Scholar · View at Scopus
  122. M. Wauters, I. Mertens, T. Rankinen, M. Chagnon, C. Bouchardt, and L. Van Gaal, “Leptin receptor gene polymorphisms are associated with insulin in obese women with impaired glucose tolerance,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 7, pp. 3227–3232, 2001. View at Publisher · View at Google Scholar · View at Scopus
  123. K. S. Park, H. D. Shin, B. L. Park et al., “Polymorphisms in the leptin receptor (LEPR)—putative association with obesity and T2DM,” Journal of Human Genetics, vol. 51, no. 2, pp. 85–91, 2006. View at Publisher · View at Google Scholar · View at Scopus
  124. A. Palou, J. Sánchez, and C. Picó, “Nutrient-gene interactions in early life programming: leptin in breast milk prevents obesity later on in life,” Advances in Experimental Medicine and Biology, vol. 646, pp. 95–104, 2009. View at Publisher · View at Google Scholar · View at Scopus
  125. F. Savino and S. A. Liguori, “Update on breast milk hormones: leptin, ghrelin and adiponectin,” Clinical Nutrition, vol. 27, no. 1, pp. 42–47, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. S. G. Bouret, “Leptin, nutrition, and the programming of hypothalamic feeding circuits,” Nestle Nutrition Workshop Series: Pediatric Program, vol. 65, pp. 25–39, 2010. View at Publisher · View at Google Scholar
  127. C. M. Phillips, L. Goumidi, S. Bertrais et al., “Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults,” Journal of Nutrition, vol. 140, no. 2, pp. 238–244, 2010. View at Publisher · View at Google Scholar · View at Scopus
  128. D. A. De Luis, R. Aller, O. Izaola, M. Gonzalez Sagrado, and R. Conde, “Influence of Lys656Asn polymorphism of leptin receptor gene on leptin response secondary to two hypocaloric diets: a randomized clinical trial,” Annals of Nutrition and Metabolism, vol. 52, no. 3, pp. 209–214, 2008. View at Publisher · View at Google Scholar · View at Scopus
  129. V. DeClercq, D. Stringer, R. Hunt, C. G. Taylor, and P. Zahradka, “Adipokine production by adipose tissue: a novel target for treating metabolic syndrome and its sequelae,” in Metabolic Syndrome: Underlying Mechanisms and Drug Therapies, M. Wang, Ed., pp. 73–131, John Wiley & Sons, Hoboken, NJ, USA, 2011. View at Google Scholar