Molecular Biology Reports

, Volume 37, Issue 3, pp 1513–1522 | Cite as

The polymorphisms of UCP1 genes associated with fat metabolism, obesity and diabetes

  • Jun-jing Jia
  • Yun-bo Tian
  • Zhen-hui Cao
  • Lin-li Tao
  • Xi Zhang
  • Si-zhen Gao
  • Chang-rong GeEmail author
  • Qiu-Ye LinEmail author
  • M. Jois


Uncoupling protein 1 (UCP1), a 32-kDa protein located in the inner mitochondrial membrane, is abundant in brown adipose tissue, as a proton transporter in mitochondria inner membrane which uncouples oxidative metabolism from ATP synthesis and dissipates energy through the heat. UCP1 has been reported to play important roles for energy homeostasis in rodents and neonate of larger mammals including human. Recently, numerous candidate genes were searched to determine the genetic factors implicated in the pathogenesis of obesity, related metabolic disorders and diabetes. UCP-1, which plays a major role in thermogenesis, was suggested to be one of the candidates. This review summarizes data supporting the existence of brown adipocytes and the role of UCP1 in energy dissipation in adult humans, and the genetic variety association with the fat metabolism, obesity and diabetes.


UCP1 Polymorphism BAT Obesity Diabetes 



The research reported herein was funded by grants from Projects: Yunnan Natural Found Project: A role for Uncoupling proteins in the control of energy utilisation in pigs (2003C0048M); The relationship of the polymorphisms of UCP2 gene and economic trait (2006C0033Q). The prophase Project 973 of the People’s Republic of China: Yunnan Wujing Pigs Meat Quality Research (2007CB116201-3). The foundation for talented man training in Yunnan Province of the People’s Republic of China (2008PY043).


  1. 1.
    Adamsa AE, Carrolla AM, Fallonb PG, Portera RK (2008) Mitochondrial uncoupling protein 1 expression in thymocytes. Biochim Biophys Acta 1777(7–8):772–776Google Scholar
  2. 2.
    Allison DB, Faith MS, Nathan JS (1996) Risch’s lambda values for human obesity. Int J Obes Relat Metab Disord 20:990–999PubMedGoogle Scholar
  3. 3.
    Banerji MA, Buckley MC, Chaiken RL, Gordon D, Lebovitz HE, Kral JG (1995) Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NIDDM. Int J Obes Relat Metab Disord 19:839–840Google Scholar
  4. 4.
    Baumruk F, Flachs P, Horakova M, Floryk D, Kopecky J (1999) Transgenic UCP1 in white adipocytes modulates mitochondrial membrane potential. FEBS Lett 444:206–210PubMedGoogle Scholar
  5. 5.
    Bouillaud F, Combes-Georges M, Ricquier D (1983) Mitochondrial of adult human brown adipose tissue contain a 32000-Mr uncoupling protein. Biosci Rep 377:5–780Google Scholar
  6. 6.
    Bouillaud F, Villarroya F, Hentz E, Raimbault S, Cassard AM, Ricquier D (1988) Detection of brown adipose tissue uncoupling protein mRNA in adult patients by a genomic probe. Clin Sci 71:291–297Google Scholar
  7. 7.
    Bouillaud F, Couplan E, Pecqueur C, Ricquier D (2001) Homologues of the uncoupling protein from brown adipose tissue (UCP-1): UCP2, UCP3, BMCP1 and UCP4. Biochim Biophys Acta 1504:107–119PubMedGoogle Scholar
  8. 8.
    Boyer B, Kozak L (1991) The mitochondrial uncoupling protein gene in brown fat: correlation between Dnase I hypersensitivity and expression in transgenic mice. Mol Cell Biol 11:4147–4156PubMedGoogle Scholar
  9. 9.
    Cassard-Doulcier AM, Bouillaud F, Mattei MG, Hentz E, Raimbault S, Thomas M, Ricquier D (1990) Human uncoupling protein gene: structure, comparison with rat gene, and assignment to the long arm of chromosome 4. J Cell Biochem 43:255–264Google Scholar
  10. 10.
    Cassard-Doulcier AM, Bouillaud F, Chagnon M, Gelly C, Dionne FT, Oppert JM, Bouchard C, Chagnon Y, Ricquier D (1996) The Bcl I polymorphism of the human uncoupling protein (UCP) gene is due to a point mutation in the 5V-flanking region. Int J Obes 20:278–279Google Scholar
  11. 11.
    Clement K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD (1995) Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med 333:352–354PubMedGoogle Scholar
  12. 12.
    Clement K, Ruiz J, Cassard-Doulcier AM, Bouillaud F, Ricquier D, Basdevant A, Guy-Grand B, Froguel P (1996) Additive effect of A → G (-3826) variant of the uncoupling protein gene and the Trp64Arg mutation of the beta 3-adrenergic receptor gene on weight gain in morbid obesity. Int J Obes Relat Metab Disord 20:1062–1066PubMedGoogle Scholar
  13. 13.
    Dalgaard LT, Pedersen O (2001) Uncoupling proteins: functional characteristics and role in the pathogenesis of obesity and type II diabetes. Diabetologia 44:946–965PubMedGoogle Scholar
  14. 14.
    Dulloo A (1999) UCP2 and UCP3: candidate genes for thermogenesis or lipid handling. Obes Matters 2:5–8Google Scholar
  15. 15.
    Elbein SC, Hasstedt SJ, Wegner K, Kahn SE (1999) Heritability of pancreatic beta-cell function among nondiabetic members of Caucasian familial type 2 diabetic kindreds. J Clin Endocrinol Metab 84:1398–1403PubMedGoogle Scholar
  16. 16.
    Esterbauer H, Oberkofler H, Liu YM, Breban D, Hell E, Krempler F, Patsch W (1998) Uncoupling protein-1 mRNA expression in obese human subjects: the role of sequence variations at the uncoupling protein-1 gene locus. J Lipid Res 39:834–844PubMedGoogle Scholar
  17. 17.
    Fogelholm M, Valve R, Kukkonen-Harjula K, Nenonen A, Hakkarainen V, Laakso M, Uusitupa M (1998) Additive effects of the mutations in the beta3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in finnish women. J Clin Endocrinol Metab 83:4246–4250PubMedGoogle Scholar
  18. 18.
    Fukuyama K, Ohara T, Hirota Y, Maeda K, Kuno S, Zenibayashi M, Teranishi T, Kouyama K, Maeda E, Sakamoto N, Kasuga M (2006) Association of the -112A > C polymorphism of the uncoupling protein 1 gene with insulin resistance in Japanese individuals with type 2 diabetes. Biochem Biophys Res Commun 339:1212–1216PubMedGoogle Scholar
  19. 19.
    Fumeron F, Durack-Bown I, Betoulle D, Cassard-Doulcier AM, Tuzet S, Bouillaud F, Melchior JC, Ricquier D, Apfelbaum M (1996) Polymorphisms of uncoupling protein (UCP) and beta 3 adrenoreceptor genes in obese people submitted to a lowcalorie diet. Int J Obes Relat Metab Disord 20:1051–1054PubMedGoogle Scholar
  20. 20.
    Gagnon J, Lago F, Chagnon YC, Perusse L, Naslund I, Lissner L, Sjostrom L, Bouchard C (1998) DNA polymorphism in the uncoupling protein 1 (UCP-1) gene has no effect on obesity related phenotypes in the Swedish obese subjects cohorts. Int J Obes Relat Metab Disord 22:500–505PubMedGoogle Scholar
  21. 21.
    Garruti G, Ricquier D (1992) Analysis of uncoupling protein and its mRNA in adipose tissue deposits of adult humans. Int J Obes Relat Metab Disord 16:383–390PubMedGoogle Scholar
  22. 22.
    Gonzalez-Barroso MD, Pecqueur C, Gelly C (2000) Transcriptional activation of the huaman ucp1 gene in a rodent cell line—synergism of retinoids, ispprotere nol, and thiazolidinedione is mediated by a multipartite response element. J Biol Chem 275:31722–31732Google Scholar
  23. 23.
    Goto TO, Takabe K, Kral JG (1995) The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects. Int J Obes Relat Metab Disord 19:841–845PubMedGoogle Scholar
  24. 24.
    Hagen T, Lowell BB (2000) Chimeric proteins between UCP1 and UCP3: the middle third of UCP1 is necessary and sufficient for activation by fatty acids. Biochem Biophys Res Commun 276:642–648PubMedGoogle Scholar
  25. 25.
    Hamman A, Benecke H, Marchand-Brustel YL, Susulic VS, Lowell BB, Flier JS (1995) Characterization of insulin resistance and NIDDM in transgenic mice with reduced brown fat. Diabetes 44:1266–1273Google Scholar
  26. 26.
    Hamann A, Tafel J, Busing B, Munzberg H, Hinney A, Mayer H, Siegfield W, Ricquier D, Greten H, Matthaei JH (1998) Analysis of the uncoupling protein-1 (UCP1) gene obese and lean subjects: identification of four amino acid variant. Int J Obes Relat Metab Disord 22:939–941PubMedGoogle Scholar
  27. 27.
    Harper M-E (1997) Obesity research continues to spring leaks. Clin Invest Med 20(4):239–244PubMedGoogle Scholar
  28. 28.
    Hasstedt SJ, Hoffman M, Leppert MF, Elbein SC (1997) Recessive inheritance of obesity in familial non-insulin-dependent diabetes mellitus, and lack of linkage to nine candidate genes. Am J Hum Genet 61:668–677PubMedGoogle Scholar
  29. 29.
    Hayakawa T, Nagai Y, Taniguchi M, Yamashita H, Takamura T, Abe T, Nomura G, Kobayashi K (1999) Phenotypic characterization of the beta3-adrenergic receptor mutation and the uncoupling protein 1 polymorphism in Japanese men. Metabolism 48:636–640PubMedGoogle Scholar
  30. 30.
    Heaton JM (1972) The distribution of brown adipose tissue in the human. J Anat 112:35–39PubMedGoogle Scholar
  31. 31.
    Heilbronn LK, Kind KL, Pancewicz E, Morris AM, Noakes M, Clifton PM (2000) Association of -3826G variant in uncoupling protein-1 with increased BMI in overweight Australian women. Diabetologia 43:242–244PubMedGoogle Scholar
  32. 32.
    Herrmann SM, Wang JG, Staessen JA, Kertmen E, Schmidt-Petersen K, Zidek W, Paul M, Brand E (2003) Uncouplin protein 1 and 3 polymorphisms are associated with waist-to-hratio. J Mol Med 81:327–332PubMedGoogle Scholar
  33. 33.
    Herskind AM, McGue M, Sørensen TIA, Harvald B (1996) Sex and age specific assessment of genetic and environmental influences on body mass indexes in twins. Int J Obes 20:106–113Google Scholar
  34. 34.
    Himms-Hagen J (1989) Brown adipose tissue thermogenesis and obesity. Prog Lipid Res 28:67–115PubMedGoogle Scholar
  35. 35.
    Himms-Hagen J, Desautels M (1978) A mitochondrial defect in brown adipose tissue if the obese (ob/ob) mouse: reduced binding of purine nucleotides and a failure to respond to cold by an binding. Biochem Biophys Res Commun 83:628–634PubMedGoogle Scholar
  36. 36.
    Houstek J, Vizek K, Pavelka S, Kopecky J, Krejcova E, Hermanska J, Cermakova M (1993) Type-II iodothyronine 5′-deiodinase and uncoupling protein in brown adipose tissue of human new brons. J Clin Endocrinol Metab 77:382–387PubMedGoogle Scholar
  37. 37.
    Huttunen P, Kortelainen MJ (1990) Long-term alcohol consumption and brown adipose tissue in man. Eur J Appl Physiol 60:418–424Google Scholar
  38. 38.
    Huttunen P, Hirvonen J, Kinnula V (1981) The occurrence of brown adipose tissue in outdoor workers. Eur J Appl Physiol 46:339–345Google Scholar
  39. 39.
    Jezek P, Garlid KD (1990) New substrates and competitive inhibitors of the Cl-translocating pathway of the uncoupling protein of brown adipose tissue mitochondria. J Biol Chem 265:19303–19311PubMedGoogle Scholar
  40. 40.
    Jezek P, Hanus J, Semrad C, Garlid KD (1996) Photoactivated fatty acid irreversible inhibits anion and proton transport through mitochondrial uncoupling protein. J Biol Chem 271:6199–6205PubMedGoogle Scholar
  41. 41.
    Kahara T, Takamura T, Hayakawa T, Nagai Y, Yamaguchi H, Katsuki T, Katsuki K, Katsuki M, Kobayashi K (2002) Prediction of exercise-mediated changes in metabolic markers by gene polymorphism. Diabetes Res Clin Pract 57(2):105–110PubMedGoogle Scholar
  42. 42.
    Kiec′-Wilk B, Wybran′ska I, Malczewska-Malec M, Leszczyn′skaGolabek I, Partyka Q, Niedbal S, Jabrpcka A, Dembinska-Kiec A (2002) Correlation of the -3826 A → G polymorphism in the promoter of the uncoupling protein 1 gene with obesity and metabolic disorders in obese families from southern Poland. J Physiol Pharmacol 53:477–490Google Scholar
  43. 43.
    Kim KS, Cho D, Kim YJ, Choi SM, Kim JY, Shin SU, Yoon YS (2005) The finding of new genetic polymorphism of UCP-1 A-1766G and its effects on body fat accumulation. Biochim Biophys Acta 1741:149–155PubMedGoogle Scholar
  44. 44.
    Kim SM, Han JH, Park HS (2006) Prevalence of low HDL-cholesterol levels and associated factors among Koreans. Circ J 70:820–826PubMedGoogle Scholar
  45. 45.
    Klaus S, Casteilla L, Bouillaud F, Ricquier D (1991) The uncoupling protein UCP: a membraneous mitochondrial ion carrier exclusively expressed in brown adipose tissue. Int J Biochem 23:791–801PubMedGoogle Scholar
  46. 46.
    Klaus S, Munzberg H, Truloff C, Heldmaier G (1998) Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature. Am J Physiol 274:R287–R293PubMedGoogle Scholar
  47. 47.
    Klingenberg M (1990) Mechanism and evolution of the uncoupling protein of brown adipose tissue. Trends Biochem Sci 15:108–112PubMedGoogle Scholar
  48. 48.
    Klinggenberg M, Huang SG (1999) Structure and function of the uncoupling protein from brown adipose tissue. Biochim Biophys Acta 1415:271–296Google Scholar
  49. 49.
    Kogure A, Yoshida T, Sakane N, Umekawa T, Takakura Y, Kondo M (1998) Synergic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on weight loss in obese Japanese. Diabetologia 41:1399PubMedGoogle Scholar
  50. 50.
    Kopecky J, Clarke G, Enerback S, Spiegelman B, Kozak LP (1995) Expression of the mitochondrial uncoupling protein gene from the aP2 promoter prevents genetic obesity. J Clin Invest 96:2914–2923PubMedGoogle Scholar
  51. 51.
    Kopecky J, Hodny Z, Rossmeisl M, Syrovy I, Kozak LP (1996) Reduction of dietary obesity in AP2-Ucp transgenic mice: physiology and adipose tissue distribution. Am J Physiol 270:E768–E775PubMedGoogle Scholar
  52. 52.
    Kopelman PG (2000) Obesity as a medical problem. Nature 404:635–643PubMedGoogle Scholar
  53. 53.
    Kortelainen ML (1996) Association between cardiac pathology and fat distribution in an autopsy series of men without premortem evidence of cardiovascular disease. Int J Obes Relat Metab Disord 20:245–252PubMedGoogle Scholar
  54. 54.
    Kortelainen ML, Pelletier G, Ricquier D, Bukowiecki LJ (1993) Immunohistochemical detection of human brown adipose tissue uncoupling protein in an autopsy series. J Histochem Cytochem 41:759–764PubMedGoogle Scholar
  55. 55.
    Kotani K, Sakane N, Saiga K, Adachi S, Shimohiro H, Mu H, Kurozawa Y (2008) Relationship between A-3826G polymorphism in the promoter of the uncoupling protein-1 gene and high-density lipoprotein cholesterol in Japanese individuals: a cross-sectional study. Arch Med Res 39(1):142–146PubMedGoogle Scholar
  56. 56.
    Kozak LP, Harper ME (2000) Mitochondrial uncoupling proteins in energy expenditure. Annu Rev Nutr 20:339–363PubMedGoogle Scholar
  57. 57.
    Krief S, Lonnqvist F, Raimbault S, Baude B, van Spronsen A, Arner P, Strosberg AD, Ricquier D, Emorine LJ (1993) Tissue distribution of b3-adrenergic receptor mRNA in man. J Clin Invest 91:344–349PubMedGoogle Scholar
  58. 58.
    Lean ME (1989) Brown adipose tissue in humans. Proc Nutr Soc 48:243–256PubMedGoogle Scholar
  59. 59.
    Lean M, James WP, Jennings G, Trayhurm P (1986) Brown adipose tissue in patients with phaeochromomcytoma. Int J Obes 10:219–227PubMedGoogle Scholar
  60. 60.
    Li B, Nolte LA, Ju JS, Han DH, Coleman T, Holloszy JO, Semenkovich CF (2000) Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice. Nat Med 6:1115–1120PubMedGoogle Scholar
  61. 61.
    Lindholma E, Klannemarka M, Agardhb E, Groopa L, Agardh CD (2004) Putative role of polymorphisms in UCP1–3 genes for diabetic nephropathy. J Diabetes Complications 18(2):103–107Google Scholar
  62. 62.
    Loncar D (1991) Convertible adipose tissue in mice. Cell Tissue Res 266:149–161PubMedGoogle Scholar
  63. 63.
    Lowell BB, Flier JS (1997) Brown adipose tissue, -3-adrenergic receptors, and obesity. Annu Rev Med 48:307–316PubMedGoogle Scholar
  64. 64.
    Lowell BB, Spiegelman BM (2000) Towards a molecular understanding of adaptive thermogenesis. Nature 404:652–659PubMedGoogle Scholar
  65. 65.
    Lowell BB, Ssusulic V, Hamann A, Lawitts JA, Himms-hagen J, Boyer BB, Kozak LP, Flier JS (1993) Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366:740–742PubMedGoogle Scholar
  66. 66.
    Luan J, Browne PO, Harding AH (2001) Evidence for gene-nutrien interaction at the PPARgamma locus. Diabetes 50:686–689PubMedGoogle Scholar
  67. 67.
    Matsushita H, Kurabayashi T, Tomita M, Kato N, Tanaka K (2003) Effects of uncoupling protein and beta3-adrenergic receptor gene polymorphisms on body size and serum lipid concentrations in Japanese women. Maturitas 45:39–45PubMedGoogle Scholar
  68. 68.
    Melnyk A, Harper ME, Himms-Hagen J (1997) Raising at thermoneutrality prevents obesity and hyperphagia in BAT-ablated transgenic mice. Am J Physiol 272:R1088–R1093PubMedGoogle Scholar
  69. 69.
    Mori H, Okazawa K, Iwamoto E, Maeda M, Hashiramoto M, Kasuga M (2001) A polymorphism in the 5′untranslated region and a Met229fi Leu variant in exon 5 of the human UCP1 gene are associated with susceptibility to type II diabetes mellitus. Diabetologia 44:373–376PubMedGoogle Scholar
  70. 70.
    Nagai N, Sakane N, Uen LM, Hamada T, Moritani T (2003) The -3826A-G variant of the uncoupling protein-1 gene diminished postprandial thermogenesis after a high fat meal in healthy boys. J Clin Endoclinol Metab 88:5661–5667Google Scholar
  71. 71.
    Nagai N, Sakane N, Fujishita A, Fujiwara R, Kimura T, Kotani K, Moritani T (2007) The -3826 A → G variant of the uncoupling protein-1 gene diminishes thermogenesis during acute cold exposure in healthy children. Obes Res Clin Pract 1(2):99–107Google Scholar
  72. 72.
    Nagase I, Yoshida T, Kumamoto K (1996) Expressing of uncoupling protein in skeletal muscle and white fat of obese mice treated with thermogenic beta 3-adrenergic agonist. J Clin Invest 97:2898–2904PubMedGoogle Scholar
  73. 73.
    Nakano T, Shinka T, Sei M, Sato Y, Umeno M, Sakamoto K (2006) A/G heterozygote of the A-3826G polymorphism in the UCP-1 gene has higher BMI than A/A and G/G homozygote in young Japanese males. J Med Invest 53:218–222PubMedGoogle Scholar
  74. 74.
    Nedergaard J, Cannon B (1992) The uncoupling protein thermogenic and mitochondrial thermogenesis. In: Ernster L (ed) New comprehensive biochemistry: moleclar mecanisms in bioenergetics. Alsevie, Amsterdam, pp 385–420Google Scholar
  75. 75.
    Nibbelink M, Moulin K, Arnaud E, Duval C, Pénicaud L, Casteilla L (2001) Brown fat UCP1 is specifically expressed in uterine longitudinal smooth muscle cells. J Biol Chem 276:47291–47295PubMedGoogle Scholar
  76. 76.
    Nicholls DG, Locke RM (1984) Thermogenic mechanisms in brow fat. Physiol Rev 64:61–64Google Scholar
  77. 77.
    Oh HH, Kim KS, Choi SM, Yang HS, Yoon Y (2004) The effects of uncoupling protein-1 genotype on lipoprotein cholesterol level in Korean obese subjects. Metabolism 53:1054–1059PubMedGoogle Scholar
  78. 78.
    Oppert JM, Vohl MC, Chagnonl M, Dionne FT, Cassard-Doulcier AM, Ricquier D, Pe ′russe L, Bouchard C (1994) DNA polymorphism in the uncoupling protein (UCP) gene and human body fat. Int J Obes 18:526–531Google Scholar
  79. 79.
    Proenza AM, Poissonnet CM, Ozata M et al (2000) Association of sets of alleles of genes encoding beta3-adrenoreceptor, uncoupling protein 1 and lipoprotein lipase with increased risk of metabolic complications in obesity. Int J Obes Relat Metab Disord 24:93–100PubMedGoogle Scholar
  80. 80.
    Ramis JM, González-Sánchez J, Proenza A, Martínez-Larrad M, Fernández-Pérez C, Palou A, Serrano-Ríos M (2004) The Arg64 allele of the β3-adrenoceptor gene but not the -3826G allele of the uncoupling protein1 geneis associated with increased leptin levels in the Spanish population1. Metabolism 53(11):1411–1416PubMedGoogle Scholar
  81. 81.
    Ravussin E et al (1988) Reduced rate of energy expenditure as a risk factor for body-weight gain. N Engl J Med 318:467–472PubMedGoogle Scholar
  82. 82.
    Ricquier D (1982) Ultrastructural and biochemical characterization of human brown adipose tissue in pheochromocytoma. J Clin Endocrinol Metab 54:803–807PubMedGoogle Scholar
  83. 83.
    Ricquier D, Bouillaud F (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J 345:161–179PubMedGoogle Scholar
  84. 84.
    Ricquier D, Bouillaud F, Toumelin P, Mory G, Bazin R, Arc J, Penicaud L (1986) Expression of uncoupling protein mRNA in ther mogenic or weakly thermogenic brown adipose tissue. Evidenc for a rapid beta-adrenoreceptor-mediated and transcriptionall regulated step during activation of thermogenesis. J Biol Chem 261:13905–13910PubMedGoogle Scholar
  85. 85.
    Rothwell NJ, Stock MJ (1979) A role for brown adipose tissue I diet-induced thermogenesis. Nature 281:31–35PubMedGoogle Scholar
  86. 86.
    Rothwell NJ, Stock MJ (1981) Influence of noradrenaline on blood flow to brown adipose tissue in rats exhibiting diet-induced thermogenesis. Pflugers Arch 389:237–242PubMedGoogle Scholar
  87. 87.
    Rothwell NJ, Stock MJ (1986) Brown adipose tissue and diet-induced thermogenesis. In: Trayhurn P, Nicholls DG (eds) Brown adipose tissue. Edward Arnold, London, pp 269–298Google Scholar
  88. 88.
    Rothwell NJ, Stoch MJ, Stribling D (1990) Diet-induced thermogenesis. In: Schonbaum E, Lomax P (eds) International encyclopoedia of pharmacology and therapeutics. Pergamon Press, Oxford, pp 309–326Google Scholar
  89. 89.
    Rudofsky G, Schroedter A, Voronko OE, Schlimme M, Tafel J, Isemann BH, Humpert PM, Morcos M, Bierhaus A, Nawroth PP, Hamann A (2006) Functional polymorphisms of UCP2 and UCP3 are associated with a reduced prevalence of diabetic neuropathy in patients with type 1 Diabetes. Diabetes Care 29:89–94PubMedGoogle Scholar
  90. 90.
    Sale MM, Hsu FC, Palmer ND, Gordon CJ, Keene KL, Borgerink HM, Sharma AJ, Bergman RN, Taylor KD, Saad MF, Norris JM (2007) The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS family study. BMC Endocr Disord 7:1–10PubMedGoogle Scholar
  91. 91.
    Saleh MC, Wheeler MB, Chan CB (2002) Uncoupling protein-2: evidence for its function as a metabolic regulator. Diabetologia 45:174–187PubMedGoogle Scholar
  92. 92.
    Schaffler A, Palitzsch KD, Watzlawek E, Drobnik W, Schwer H, Scholmerich J, Schmitz G (1999) Frequency and significance of the A → G (-3826) polymorphism in the promoter of the gene for uncoupling protein-1 with regard to metabolic parameters and adipocyte transcription factor binding in a large population-based Caucasian cohort. Eur J Clin Invest 29:770–779PubMedGoogle Scholar
  93. 93.
    Shihara N, Yasuda K, Moritani T et al (2001) Synergistic effects of polymorphisms of uncoupling protein 1 and beta3-adrenergic receptor genes on autonomic nervous system activity. Int J Obes Relat Metab Disord 25:761–766PubMedGoogle Scholar
  94. 94.
    Shin HD, Kim KS, Cha MH, Yoon Y (2005) The effects of UCP-1 polymorphisms on obesity phenotypes among Korean female subjects. Biochem Biophys Res Commun 335(2):624–630PubMedGoogle Scholar
  95. 95.
    Shuldiner AR, Silver K, Roth J, Walston J (1996) Beta 3-adrenoceptor gene variant in obesity and insulin resistance. Lancet 348:1584–1585PubMedGoogle Scholar
  96. 96.
    Silva JE, Rabelo R (1997) Regulation of the uncoupling protein gene expression. Eur J Endocrinol 136:251–264PubMedGoogle Scholar
  97. 97.
    Skulachev VP (1991) Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation. FEBS Lett 294:158–162PubMedGoogle Scholar
  98. 98.
    Smith RE, Horwitz BA (1969) Brown fat and thermogenesis. Physio Rev 49:330–425Google Scholar
  99. 99.
    Sørensen TIA, Price RA, Stunkard AJ, Schulsinger F (1989) Genetics of obesity in adults adoptees and their biological siblings. Br Med J 298:87–90Google Scholar
  100. 100.
    Stefl B, Janovska A, Hodny Z, Rossmeisl M, Horakova M, Syrovy I, Bemova J, Bendlova B, Kopecky J (1998) Brown fat is essential for cold-induced thermogenesis but not for obesity resistance in aP2-Ucp mice. Am J Physiol 274:E527–E533PubMedGoogle Scholar
  101. 101.
    Stock MJ (1989) The role of brown adipose tissue in diet-induced thermogenesis. Proc Nutr Soc 48:189–196PubMedGoogle Scholar
  102. 102.
    Stock MJ (1999) Gluttony and thermogenesis revisited. Int J Obes Relat Metab Disord 23:1105–1117PubMedGoogle Scholar
  103. 103.
    Stunkard AJ, Sørensen TIA, Hanis C et al (1986) An adoption study of human obesity. N Engl J Med 314:193–198PubMedGoogle Scholar
  104. 104.
    Stunkard AJ, Harris JR, Pedersen NL, McClearn GE (1990) The body-mass indeks of twins who have been reared apart. N Engl J Med 322:1483–1487PubMedGoogle Scholar
  105. 105.
    Trayhurn P (1990) Energy expenditure and thermogenesis: animal studies on brown adipose tissue. Int J Obes 14:17–26PubMedGoogle Scholar
  106. 106.
    Trayhurn P, Nicholls DG (1986) Brown adipose tissue. Edward Arnold, LondonGoogle Scholar
  107. 107.
    Trayhurn P, Jones PM, McGuckin MM, Goodbody AE (1982) Effects of overfeeding on energy balance and brown fat thermogenesis in obese (ob/ob) mice. Nature 295:323–325PubMedGoogle Scholar
  108. 108.
    Urhammer SA, Fridberg M, Sørensen TI, Echwald SM, Andersen T, Tybjærg-Hansen A, Clausen JO, Pedersen O (1997) Studies of genetic variability of the uncoupling protein 1 gene in Caucasian subjects with juvenile-onset obesity. J Clin Endocrinol Metab 82:4069–4074PubMedGoogle Scholar
  109. 109.
    Valve R, Heikkinen S, Rissanen A, Laakso M, Uusitupa M (1998) Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on basal metabolic rate in obes Finns. Diabetologia 41:357–361PubMedGoogle Scholar
  110. 110.
    Vogler GP, Sørensen TIA, Stunkard AJ, Srinivasan MR, Rao DC (1995) Influences of genes and shared family environment on adult body mass indeks assessed in an adoption study by a comprehensive path model. Int J Obes Rel Met Disor 19:40–45Google Scholar
  111. 111.
    Walston J, Silver K, Bogardus C, Knowler WC, Celi FS, Austin S, Manning B, Strosberg AD, Stern MP, Raben N (1995) Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic-receptor gene. N Engl J Med 333:343–347PubMedGoogle Scholar
  112. 112.
    Weyer C, Bogardus C, Mott DM, Pratley RE (1999) The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104:787–794PubMedGoogle Scholar
  113. 113.
    Widen E, Lehto M, Kanninen T, Walston J, Shuldiner AR, Groop LC (1995) Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med 333:348–351PubMedGoogle Scholar
  114. 114.
    Zancanaro C, Pelosi G, Accordini C, Balercia G, Sbabo L, Cinti S (1994) Immunohistochemical identification of the uncoupling protein in human hibernoma. Biol Cell 80:75–78PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Jun-jing Jia
    • 1
  • Yun-bo Tian
    • 2
  • Zhen-hui Cao
    • 1
  • Lin-li Tao
    • 1
  • Xi Zhang
    • 1
  • Si-zhen Gao
    • 1
  • Chang-rong Ge
    • 1
    Email author
  • Qiu-Ye Lin
    • 1
    Email author
  • M. Jois
    • 3
  1. 1.Yunnan Provincial Laboratory of Animal Nutrition and Feed ScienceYunnan Agricultural UniversityKunmingPeople’s Republic of China
  2. 2.College of ZhongKai Agricultural Technology and ScienceGuangzhouPeople’s Republic of China
  3. 3.Department of Agriculture, School of Life SciencesLa Trobe UniversityBundooraAustralia

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