Genetic background of aberrant thermogenin expression (UCP1) in obesity leading to metabolic syndrome

COMMENTARY ON THE LAW

Genetic background of aberrant thermogenin expression (UCP1) in obesity leading to metabolic syndrome

Małgorzata Stosio 1 , Agata Witkowicz 1 , Anna Kowalska 2 , Lidia Karabon 1

1. Instytut Immunologii i Terapii Doświadczalnej PAN im. L. Hirszfelda we Wrocławiu
2. Instytut Immunologii i Terapii Doświadczalnej PAN im. L. Hirszfelda we Wrocławiu; Insytut Genetyki Człowieka PAN w Poznaniu

Published: 2016-12-31
DOI: 10.5604/17322693.1227677
GICID: 01.3001.0009.6915
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2016; 70 : 1389-1403

 

Abstract

Cardiovascular and metabolic disturbances individually and interdependently lead to chronic pathological conditions observed in cardio-metabolic diseases (CMDs). In Europe, the morbidity and mortality caused by cardiovascular disease are the highest among all diseases. Therefore, it seems important to search for new and alternative therapies for obesity, which is the main cause of type 2 diabetes (T2D) and cardiovascular disease (CD). Great attention has been paid to the role of brown adipose tissue in fat burning and the possibility of transformation of the white adipose tissue to cells with brown adipose tissue function as a potential form of treatment of obesity. The best-characterized marker of brown adipose tissue is uncoupling protein 1 (UCP1), which has the ability to dissipate energy as heat in the process called non-shivering thermogenesis. Numerous studies have shown that altered expression of this protein can lead to disturbances in fat metabolism. One possible reason for the aberrant expression of UCP1 may be inherited variations in the gene encoding that protein. Therefore, several studies investigating the role of polymorphisms in the gene encoding UCP1 in susceptibility to obesity or metabolic syndrome have been performed. Here we summarize the results of studies describing the associations between the UCP1 gene polymorphisms A-3826G, A-1766G, Met229Leu and Ala64Thr and polymorphism Trp64Arg in the β3-AR gene, their correlations and their associations with the occurrence of metabolic syndrome.

References

  • 1. Arciero P.J., Gentile C.L., Martin-Pressman R., Ormsbee M.J., EverettM., Zwicky L., Steele C.A.: Increased dietary protein and combinedhigh intensity aerobic and resistance exercise improves bodyfat distribution and cardiovascular risk factors. Int. J. Sport Nutr.Exerc. Metab., 2006; 16: 373-392
    Google Scholar
  • 2. Azzu V., Brand M.D.: The on-off switches of the mitochondrialuncoupling proteins. Trends Biochem. Sci., 2010; 35: 298-307
    Google Scholar
  • 3. Berg J.M., Tymoczko J.L., Stryer L.: Fosforylacja oksydacyjna, Biochemia.red. Szweykowska-Kulińska Z., Jarmołowski A., WydawnictwoNaukowe PWN, Warszawa 2009; 530-533
    Google Scholar
  • 4. Bostrom P., Wu J., Jedrychowski M.P., Korde A., Ye L., Lo J.C., RasbachK.A., Bostrom E.A., Choi J.H., Long J.Z., Kajimura S., ZingarettiM.C., Vind B.F., Tu H., Cinti S., Hojlund K., Gygi S.P., Spiegelman B.M.:A PGC1-α-dependent myokine that drives brown-fat-like developmentof white fat and thermogenesis. Nature, 2012; 481: 463-468
    Google Scholar
  • 5. Brand M.D., Affourtit C., Esteves T.C., Green K., Lambert A.J.,Miwa S., Pakay J.L., Parker N.: Mitochondrial superoxide: production,biological effects, and activation of uncoupling proteins. FreeRadic. Biol. Med., 2004; 37: 755-767
    Google Scholar
  • 6. Brondani L.A., Assmann T.S., Duarte G.C., Gross J.L., Canani L.H.,Crispim D.: The role of the uncoupling protein 1 (UCP1) on the developmentof obesity and type 2 diabetes mellitus. Arq. Bras. Endocrinol.Metabol., 2012; 56: 215-225
    Google Scholar
  • 7. Cannon B., Nedergaard J.: Brown adipose tissue: function andphysiological significance. Physiol. Rev., 2004; 84: 277-359
    Google Scholar
  • 8. Carey D.G.: Abdominal obesity. Curr. Opin. Lipidol., 1998; 9: 35-40
    Google Scholar
  • 9. Carey V.J., Walters E.E., Colditz G.A., Solomon C.G., Willett W.C.,Rosner B.A., Speizer F.E., Manson J.E.: Body fat distribution and riskof non-insulin-dependent diabetes mellitus in women. The Nurses’Health Study. Am. J. Epidemiol., 1997; 145: 614-619
    Google Scholar
  • 10. Cassard-Doulcier A.M., Bouillaud F., Chagnon M., Gelly C., DionneF.T., Oppert J.M., Bouchard C., Chagnon Y., Ricquier D.: TheBcl I polymorphism of the human uncoupling protein (ucp) gene isdue to a point mutation in the 5’-flanking region. Int. J. Obes. Relat.Metab. Disord., 1996; 20: 278-279
    Google Scholar
  • 11. Castro J.P., El-Atat F.A., McFarlane S.I., Aneja A., Sowers J.R.:Cardiometabolic syndrome: pathophysiology and treatment. Curr.PiśmiennictwoHypertens. Rep., 2003; 5: 393-401
    Google Scholar
  • 12. Cederberg A., Gronning L.M., Ahren B., Tasken K., Carlsson P.,Enerback S.: FOXC2 is a winged helix gene that counteracts obesity,hypertriglyceridemia, and diet-induced insulin resistance. Cell,2001; 106: 563-573
    Google Scholar
  • 13. Chechi K., Carpentier A.C., Richard D.: Understanding the brownadipocyte as a contributor to energy homeostasis. Trends Endocrinol.Metab., 2013; 24: 408-420
    Google Scholar
  • 14. Chicco A.J., Sparagna G.C.: Role of cardiolipin alterations in mitochondrialdysfunction and disease. Am. J. Physiol. Cell Physiol.,2007; 292: C33-C44
    Google Scholar
  • 15. Clement K., Ruiz J., Cassard-Doulcier A.M., Bouillaud F., RicquierD., Basdevant A., Guy-Grand B., Froguel P.: Additive effect of A–>G(-3826) variant of the uncoupling protein gene and the Trp64Argmutation of the β3-adrenergic receptor gene on weight gain in morbidobesity. Int. J. Obes. Relat. Metab. Disord., 1996; 20: 1062-1066
    Google Scholar
  • 16. Cypess A.M., Lehman S., Williams G., Tal I., Rodman D., GoldfineA.B., Kuo F.C., Palmer E.L., Tseng Y.H., Doria A., Kolodny G.M., KahnC.R.: Identification and importance of brown adipose tissue in adulthumans. N. Engl. J. Med., 2009; 360: 1509-1517
    Google Scholar
  • 17. Dalgaard L.T., Pedersen O.: Uncoupling proteins: functionalcharacteristics and role in the pathogenesis of obesity and Type IIdiabetes. Diabetologia, 2001; 44: 946-965
    Google Scholar
  • 18. Del Mar Gonzales-Barroso M., Ricquier D., Cassard-DoulcierA.M.: The human uncoupling protein-1 gene (UCP1): present statusand perspectives in obesity research. Obes. Rev., 2000; 1: 61-72
    Google Scholar
  • 19. Du Y., Meng Q., Zhang Q., Guo F.: Isoleucine or valine deprivationstimulates fat loss via increasing energy expenditure and regulatinglipid metabolism in WAT. Amino Acids, 2012; 43: 725-734
    Google Scholar
  • 20. Echtay K.S.: Mitochondrial uncoupling proteins – what is theirphysiological role? Free Radic. Biol. Med., 2007; 43: 1351-1371
    Google Scholar
  • 21. Echtay K.S., Esteves T.C., Pakay J.L., Jekabsons M.B., Lambert A.J.,Portero-Otin M., Pamplona R., Vidal-Puig A.J., Wang S., Roebuck S.J.,Brand M.D.: A signalling role for 4-hydroxy-2-nonenal in regulationof mitochondrial uncoupling. EMBO J., 2003; 22: 4103-4110
    Google Scholar
  • 22. Echtay K.S., Roussel D., St-Pierre J., Jekabsons M.B., Cadenas S., Stuart J.A., Harper J.A., Roebuck S.J., Morrison A., Pickering S.,Clapham J.C., Brand M.D.: Superoxide activates mitochondrial uncouplingproteins. Nature, 2002; 415: 96-99
    Google Scholar
  • 23. Elbein S.C., Hasstedt S.J., Wegner K., Kahn S.E.: Heritability ofpancreatic β-cell function among nondiabetic members of Caucasianfamilial type 2 diabetic kindreds. J. Clin. Endocrinol. Metab.,1999; 84: 1398-1403
    Google Scholar
  • 24. Esterbauer H., Oberkofler H., Liu Y.M., Breban D., Hell E., KremplerF., Patsch W.: Uncoupling protein-1 mRNA expression in obesehuman subjects: the role of sequence variations at the uncouplingprotein-1 gene locus. J. Lipid Res., 1998; 39: 834-844
    Google Scholar
  • 25. Fedorenko A., Lishko P.V., Kirichok Y.: Mechanism of fattyacid-dependentUCP1 uncoupling in brown fat mitochondria. Cell,2012; 151: 400-413
    Google Scholar
  • 26. Fisher M.: Cardiometabolic disease: the new challenge? Pract.Diab. Int., 2006; 23: 95-97
    Google Scholar
  • 27. Fisher F.M., Maratos-Flier E.: Stress heats up the adipocyte. Nat.Med., 2013; 19: 17-18
    Google Scholar
  • 28. Fisler J.S., Warden C.H.: Uncoupling proteins, dietary fat andthe metabolic syndrome. Nutr. Metab., 2006; 3: 38
    Google Scholar
  • 29. Fogelholm M., Valve R., Kukkonen-Harjula K., Nenonen A., HakkarainenV., Laakso M., Uusitupa M.: Additive effects of the mutationsin the β3-adrenergic receptor and uncoupling protein-1 geneson weight loss and weight maintenance in Finnish women. J. Clin.Endocrinol. Metab., 1998; 83: 4246-4250
    Google Scholar
  • 30. Forga L., Corbalan M., Marti A., Fuentes C., Martinez-GonzalezM.A., Martinez A.: Influence of the polymorphism 03826 A–>G inthe UCP1 gene on the components of metabolic syndrome. An. Sist.Sanit. Navar., 2003; 26: 231-236
    Google Scholar
  • 31. Fumeron F., Durack-Bown I., Betoulle D., Cassard-Doulcier A.M.,Tuzet S., Bouillaud F., Melchior J.C., Ricquier D., Apfelbaum M.: Polymorphismsof uncoupling protein (UCP) and β3 adrenoreceptorgenes in obese people submitted to a low calorie diet. Int. J. Obes.Relat. Metab. Disord., 1996; 20: 1051-1054
    Google Scholar
  • 32. Gagnon J., Lago F., Chagnon Y.C., Perusse L., Naslund I., Lissner L.,Sjostrom L., Bouchard C.: DNA polymorphism in the uncoupling protein 1 (UCP1) gene has no effect on obesity related phenotypes in the SwedishObese Subjects cohorts. Int. J. Obes. Relat. Metab. Disord., 1998; 22: 500-505
    Google Scholar
  • 33. Gagnon J., Mauriege P., Roy S., Sjostrom D., Chagnon Y.C., DionneF.T., Oppert J.M., Perusse L., Sjostrom L., Bouchard C.: The Trp64Argmutation of the β3 adrenergic receptor gene has no effect on obesityphenotypes in the Quebec Family Study and Swedish Obese Subjectscohorts. J. Clin. Invest, 1996; 98: 2086-2093
    Google Scholar
  • 34. Haines T.H.: A new look at Cardiolipin. Biochim. Biophys. Acta,2009; 1788: 1997-2002
    Google Scholar
  • 35. Hamann A., Tafel J., Busing B., Munzberg H., Hinney A., MayerH., Siegfried W., Ricquier D., Greten H., Hebebrand J., Matthaei S.:Analysis of the uncoupling protein-1 (UCP1) gene in obese and leansubjects: identification of four amino acid variants. Int. J. Obes. Relat.Metab. Disord., 1998; 22: 939-941
    Google Scholar
  • 36. Hasek B.E., Stewart L.K., Henagan T.M., Boudreau A., LenardN.R., Black C., Shin J., Huypens P., Malloy V.L., Plaisance E.P., KrajcikR.A., Orentreich N., Gettys T.W.: Dietary methionine restrictionenhances metabolic flexibility and increases uncoupled respirationin both fed and fasted states. Am. J. Physiol. Regul. Integr. Comp.Physiol., 2010; 299: R728-R739
    Google Scholar
  • 37. Hasstedt S.J., Hoffman M., Leppert M.F., Elbein S.C.: Recessiveinheritance of obesity in familial non-insulin-dependent diabetesmellitus, and lack of linkage to nine candidate genes. Am. J. Hum.Genet., 1997; 61: 668-677
    Google Scholar
  • 38. Hayakawa T., Nagai Y., Taniguchi M., Yamashita H., TakamuraT., Abe T., Nomura G., Kobayashi K.: Phenotypic characterization ofthe β3-adrenergic receptor mutation and the uncoupling protein 1 polymorphism in Japanese men. Metabolism, 1999; 48: 636-640
    Google Scholar
  • 39. Heaton J.M.: The distribution of brown adipose tissue in thehuman. J. Anat., 1972; 112: 35-39
    Google Scholar
  • 40. Heilbronn L.K., Kind K.L., Pancewicz E., Morris A.M., Noakes M.,Clifton P.M.: Association of – 3826 G variant in uncoupling protein-1with increased BMI in overweight Australian women. Diabetologia,2000; 43: 242-244
    Google Scholar
  • 41. Hellmer J., Marcus C., Sonnenfeld T., Arner P.: Mechanisms fordifferences in lipolysis between human subcutaneous and omentalfat cells. J. Clin. Endocrinol. Metab., 1992; 75: 15-20
    Google Scholar
  • 42. Herrmann S.M., Wang J.G., Staessen J.A., Kertmen E., Schmidt–Petersen K., Zidek W., Paul M., Brand E.: Uncoupling protein 1 and 3polymorphisms are associated with waist-to-hip ratio. J. Mol. Med.,2003; 81: 327-332
    Google Scholar
  • 43. Herskind A.M., McGue M., Sorensen T.I., Harvald B.: Sex andage specific assessment of genetic and environmental influences onbody mass index in twins. Int. J. Obes. Relat. Metab. Disord., 1996;20: 106-113
    Google Scholar
  • 44. Himms-Hagen J., Desautels M.: A mitochondrial defect in brownadipose tissue of the obese (ob/ob) mouse: reduced binding of purinenucleotides and a failure to respond to cold by an increase in binding.Biochem. Biophys. Res. Commun., 1978; 83: 628-634
    Google Scholar
  • 45. Hoang T., Smith M.D., Jelokhani-Niaraki M.: Expression, folding,and proton transport activity of human uncoupling protein-1 (UCP1)in lipid membranes: evidence for associated functional forms. J. Biol.Chem., 2013; 288: 36244-36258
    Google Scholar
  • 46. Hoang T., Smith M.D., Jelokhani-Niaraki M.: Toward understandingthe mechanism of ion transport activity of neuronal uncouplingproteins UCP2, UCP4, and UCP5. Biochemistry, 2012; 51: 4004-4014
    Google Scholar
  • 47. Iwata K., Iwasa M., Nakatani T., Yano Y., Mifuji-Moroka R., HaraN., Akamatsu M., Ishidome M., Takei Y.: Seasonal variation in visceralfat and blood HbA1c in people with type 2 diabetes. Diabetes Res.Clin. Pract., 2012; 96: e53-e54
    Google Scholar
  • 48. Jia J.J., Tian Y.B., Cao Z.H., Tao L.L., Zhang X., Gao S.Z., Ge C.R., LinQ.Y., Jois M.: The polymorphisms of UCP1 genes associated with fatmetabolism, obesity and diabetes. Mol. Biol. Rep., 2010; 37: 1513-1522
    Google Scholar
  • 49. Kajimura S., Saito M.: A new era in brown adipose tissue biology:molecular control of brown fat development and energy homeostasis.Annu. Rev. Physiol., 2014; 76: 225-249
    Google Scholar
  • 50. Keipert S., Jastroch M.: Brite/beige fat and UCP1 – is it thermogenesis?Biochim. Biophys. Acta, 2014; 1837: 1075-1082
    Google Scholar
  • 51. Kiec-Wilk B., Wybranska I., Malczewska-Malec M., LeszczynskaGolabekL., Partyka L., Niedbal S., Jabrocka A., Dembinska-Kiec A.:Correlation of the – 3826A >G polymorphism in the promoter of theuncoupling protein 1 gene with obesity and metabolic disorders inobese families from southern Poland. J. Physiol. Pharmacol., 2002;53: 477-490
    Google Scholar
  • 52. Kim K.S., Cho D.Y., Kim Y.J., Choi S.M., Kim J.Y., Shin S.U., YoonY.S.: The finding of new genetic polymorphism of UCP-1 A-1766Gand its effects on body fat accumulation. Biochim. Biophys. Acta,2005; 1741: 149-155
    Google Scholar
  • 53. Klaus S., Casteilla L., Bouillaud F., Ricquier D.: The uncouplingprotein UCP: a membraneous mitochondrial ion carrier exclusivelyexpressed in brown adipose tissue. Int. J. Biochem., 1991; 23: 791-801
    Google Scholar
  • 54. Klaus S., Ely M., Encke D., Heldmaier G.: Functional assessmentof white and brown adipocyte development and energy metabolismin cell culture. Dissociation of terminal differentiation and thermogenesisin brown adipocytes. J. Cell Sci., 1995; 108: 3171-3180
    Google Scholar
  • 55. Klingenberg M.: Cardiolipin and mitochondrial carriers. Biochim.Biophys. Acta, 2009; 1788: 2048-2058
    Google Scholar
  • 56. Klingenberg M.: Uncoupling proteins – how do they work andhow are they regulated. IUBMB Life, 2001; 52: 175-179
    Google Scholar
  • 57. Kogure A., Yoshida T., Sakane N., Umekawa T., Takakura Y.,Kondo M.: Synergic effect of polymorphisms in uncoupling protein 1 and β3-adrenergic receptor genes on weight loss in obese Japanese.Diabetologia, 1998; 41: 1399
    Google Scholar
  • 58. Koh Y.J., Park B.H., Park J.H., Han J., Lee I.K., Park J.W., KohG.Y.: Activation of PPAR g induces profound multilocularization ofadipocytes in adult mouse white adipose tissues. Exp. Mol. Med.,2009; 41: 880-895
    Google Scholar
  • 59. Kopelman P.G.: Obesity as a medical problem. Nature, 2000;404: 635-643
    Google Scholar
  • 60. Kozak L.P., Harper M.E.: Mitochondrial uncoupling proteins inenergy expenditure. Annu. Rev. Nutr., 2000; 20: 339-363
    Google Scholar
  • 61. Kozak L.P., Anunciado-Koza R.: UCP1: its involvement and utilityin obesity. Int. J. Obes., 2008; 32, Suppl. 7: S32-S38
    Google Scholar
  • 62. Kramarova T.V., Shabalina I.G., Andersson U., Westerberg R.,Carlberg I., Houstek J., Nedergaard J., Cannon B.: Mitochondrial ATPsynthase levels in brown adipose tissue are governed by the c-Fosubunit P1 isoform. FASEB J., 2008; 22: 55-63
    Google Scholar
  • 63. Krauss S., Zhang C.Y., Lowell B.B.: The mitochondrial uncoupling-proteinhomologues. Nat. Rev. Mol. Cell Biol., 2005; 6: 248-261
    Google Scholar
  • 64. Kuhn E., Binart N., Lombes M.: Brown, white, beige: the color offat and new therapeutic perspectives for obesity. Ann. Endocrinol.,2012; 73, Suppl. 1: S2-S8
    Google Scholar
  • 65. Kurabayashi T., Carey D.G., Morrison N.A.: The β3-adrenergicreceptor gene Trp64Arg mutation is overrepresented in obese women.Effects on weight, BMI, abdominal fat, blood pressure, andreproductive history in an elderly Australian population. Diabetes,1996; 45: 1358-1363
    Google Scholar
  • 66. Lean M.E.: Brown adipose tissue in humans. Proc. Nutr. Soc.,1989; 48: 243-256
    Google Scholar
  • 67. Lidell M.E., Betz M.J., Dahlqvist L.O., Heglind M., Elander L.,Slawik M., Mussack T., Nilsson D., Romu T., Nuutila P., Virtanen K.A.,Beuschlein F., Persson A., Borga M., Enerback S.: Evidence for twotypes of brown adipose tissue in humans. Nat. Med., 2013; 19: 631-634
    Google Scholar
  • 68. Lim J.H., Ko M.M., Moon T.W., Cha M.H., Lee M.S.: Association ofthe UCP-1 single nucleotide polymorphism A-3826G with the dampness-phlegmpattern among Korean stroke patients. BMC Complement.Altern. Med., 2012; 12: 180
    Google Scholar
  • 69. Lonnqvist F., Krief S., Strosberg A.D., Nyberg S., Emorine L.J.,Arner P.: Evidence for a functional β3-adrenoceptor in man. Br. J.Pharmacol., 1993; 110: 929-936
    Google Scholar
  • 70. Manieri M., Murano I., Fianchini A., Brunelli A., Cinti S.: Morphologicaland immunohistochemical features of brown adipocytesand preadipocytes in a case of human hibernoma. Nutr. Metab. Cardiovasc.Dis., 2010; 20: 567-574
    Google Scholar
  • 71. Meyer C.W., Willershauser M., Jastroch M., Rourke B.C., FrommeT., Oelkrug R., Heldmaier G., Klingenspor M.: Adaptive thermogenesisand thermal conductance in wild-type and UCP1-KO mice.Am. J. Physiol. Regul. Integr. Comp. Physiol., 2010; 299: R1396-R1406
    Google Scholar
  • 72. Mori H., Okazawa H., Iwamoto K., Maeda E., Hashiramoto M., KasugaM.: A polymorphism in the 5’ untranslated region and a Met229—>Leu variant in exon 5 of the human UCP1 gene are associatedwith susceptibility to type II diabetes mellitus. Diabetologia, 2001;44: 373-376
    Google Scholar
  • 73. Morita E., Taniguchi H., Sakaue M.: Trp64Arg polymorphism inβ3-adrenergic receptor gene is associated with decreased fat oxidationboth in resting and aerobic exercise in the Japanese male. Exp.Diabetes Res., 2009; 2009: 605139
    Google Scholar
  • 74. Nagase T., Aoki A., Yamamoto M., Yasuda H., Kado S., NishikawaM., Kugai N., Akatsu T., Nagata N.: Lack of association between theTrp64 Arg mutation in the β3-adrenergic receptor gene and obesityin Japanese men: a longitudinal analysis. J. Clin. Endocrinol. Metab., 1997; 82: 1284-1287
    Google Scholar
  • 75. Nakano T., Shinka T., Sei M., Sato Y., Umeno M., Sakamoto K.,Nomura I., Nakahori Y.: A/G heterozygote of the A-3826G polymorphismin the UCP-1 gene has higher BMI than A/A and G/G homozygotein young Japanese males. J. Med. Invest, 2006; 53: 218-222
    Google Scholar
  • 76. Nakayama K., Miyashita H., Yanagisawa Y., Iwamoto S.: Seasonaleffects of UCP1 gene polymorphism on visceral fat accumulation inJapanese adults. PLoS One, 2013; 8: e74720
    Google Scholar
  • 77. Nedergaard J., Cannon B.: UCP1 mRNA does not produce heat.Biochim. Biophys. Acta, 2013; 1831: 943-949
    Google Scholar
  • 78. Nicholls D.G., Locke R.M.: Thermogenic mechanisms in brownfat. Physiol. Rev., 1984; 64: 1-64
    Google Scholar
  • 79. Nichols M., Townsend N., Scarborough P., Rayner M.: Cardiovasculardisease in Europe 2014: epidemiological update. Eur. HeartJ., 2014; 35: 2929
    Google Scholar
  • 80. Oppert J.M., Vohl M.C., Chagnon M., Dionne F.T., Cassard-DoulcierA.M., Ricquier D., Perusse L., Bouchard C.: DNA polymorphismin the uncoupling protein (UCP) gene and human body fat. Int. J.Obes. Relat. Metab. Disord., 1994; 18: 526-531
    Google Scholar
  • 81. Ouellet V., Routhier-Labadie A., Bellemare W., Lakhal-Chaieb L.,Turcotte E., Carpentier A.C., Richard D.: Outdoor temperature, age,sex, body mass index, and diabetic status determine the prevalence,mass, and glucose-uptake activity of 18F-FDG-detected BAT inhumans. J. Clin. Endocrinol. Metab., 2011; 96: 192-199
    Google Scholar
  • 82. Pfannenberg C., Werner M.K., Ripkens S., Stef I., Deckert A.,Schmadl M., Reimold M., Haring H.U., Claussen C.D., Stefan N.: Impactof age on the relationships of brown adipose tissue with sexand adiposity in humans. Diabetes, 2010; 59: 1789-1793
    Google Scholar
  • 83. Pfeiffer K., Gohil V., Stuart R.A., Hunte C., Brandt U., GreenbergM.L., Schagger H.: Cardiolipin stabilizes respiratory chain supercomplexes.J. Biol. Chem., 2003; 278: 52873-52880
    Google Scholar
  • 84. Pischon T., Boeing H., Hoffmann K., Bergmann M., Schulze M.B.,Overvad K., van der Schouw Y.T., Spencer E., Moons K.G., TjonnelandA., Halkjaer J., Jensen M.K., Stegger J., Clavel-Chapelon F., Boutron–Ruault M.C. i wsp.: General and abdominal adiposity and risk ofdeath in Europe. N. Engl. J. Med., 2008; 359: 2105-2120
    Google Scholar
  • 85. Plaisance E.P., Henagan T.M., Echlin H., Boudreau A., Hill K.L., LenardN.R., Hasek B.E., Orentreich N., Gettys T.W.: Role of β-adrenergicreceptors in the hyperphagic and hypermetabolic responses to dietarymethionine restriction. Am. J. Physiol Regul. Integr. Comp. Physiol.,2010; 299: R740-R750
    Google Scholar
  • 86. Pownall M.E., Gustafsson M.K., Emerson C.P.Jr.: Myogenic regulatoryfactors and the specification of muscle progenitors in vertebrateembryos. Annu. Rev. Cell Dev. Biol., 2002; 18: 747-783
    Google Scholar
  • 87. Proenza A.M., Poissonnet C.M., Ozata M., Ozen S., Guran S., PalouA., Strosberg A.D.: Association of sets of alleles of genes encodingβ3-adrenoreceptor, uncoupling protein 1 and lipoprotein lipase withincreased risk of metabolic complications in obesity. Int. J. Obes. Relat.Metab. Disord., 2000; 24: 93-100
    Google Scholar
  • 88. Rajan S., Gupta A., Beg M., Shankar K., Srivastava A., VarshneyS., Kumar D., Gaikwad A.N.: Adipocyte transdifferentiation and itsmolecular targets. Differentiation, 2014; 87: 183-192
    Google Scholar
  • 89. Ramis J.M., Gonzalez-Sanchez J.L., Proenza A.M., Martinez-LarradM.T., Fernandez-Perez C., Palou A., Serrano-Rios M.: The Arg64allele of the β3-adrenoceptor gene but not the – 3826G allele of theuncoupling protein 1 gene is associated with increased leptin levelsin the Spanish population. Metabolism, 2004; 53: 1411-1416
    Google Scholar
  • 90. Ricquier D.: Respiration uncoupling and metabolism in the controlof energy expenditure. Proc. Nutr. Soc., 2005; 64: 47-52
    Google Scholar
  • 91. Roman S., Agil A., Peran M., Alvaro-Galue E., Ruiz-Ojeda F.J.,Fernandez-Vazquez G., Marchal J.A.: Brown adipose tissue and noveltherapeutic approaches to treat metabolic disorders. Transl. Res., 2015; 165: 464-479
    Google Scholar
  • 92. Saely C.H., Geiger K., Drexel H.: Brown versus white adiposetissue: a mini-review. Gerontology, 2012; 58: 15-23
    Google Scholar
  • 93. Saitoh S., Shimoda T., Hamamoto Y., Nakaya Y., Nakajima S.:Correlations among obesity-associated gene polymorphisms, bodycomposition, and physical activity in patients with type 2 diabetesmellitus. Indian J. Endocrinol. Metab., 2015; 19: 66-71
    Google Scholar
  • 94. Saltiel A.R., Kahn C.R.: Insulin signalling and the regulation ofglucose and lipid metabolism. Nature, 2001; 414: 799-806
    Google Scholar
  • 95. Schaffler A., Palitzsch K.D., Watzlawek E., Drobnik W., SchwerH., Scholmerich J., Schmitz G.: Frequency and significance of theA–>G (-3826) polymorphism in the promoter of the gene for uncouplingprotein-1 with regard to metabolic parameters and adipocytetranscription factor binding in a large population-based Caucasiancohort. Eur. J. Clin. Invest, 1999; 29: 770-779
    Google Scholar
  • 96. Schlame M., Towbin J.A., Heerdt P.M., Jehle R., DiMauro S., BlanckT.J.: Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome. Ann.Neurol., 2002; 51: 634-637
    Google Scholar
  • 97. Schulz T.J., Huang P., Huang T.L., Xue R., McDougall L.E., TownsendK.L., Cypess A.M., Mishina Y., Gussoni E., Tseng Y.H.: Brown–fat paucity due to impaired BMP signalling induces compensatorybrowning of white fat. Nature, 2013; 495: 379-383
    Google Scholar
  • 98. Shin H.D., Kim K.S., Cha M.H., Yoon Y.: The effects of UCP-1 polymorphismson obesity phenotypes among Korean female subjects.Biochem. Biophys. Res. Commun., 2005; 335: 624-630
    Google Scholar
  • 99. Sivenius K., Valve R., Lindi V., Niskanen L., Laakso M., UusitupaM.: Synergistic effect of polymorphisms in uncoupling protein 1and β3-adrenergic receptor genes on long-term body weight changein Finnish type 2 diabetic and non-diabetic control subjects. Int.J. Obes. Relat. Metab. Disord., 2000; 24: 514-519
    Google Scholar
  • 100. Sorensen T.I., Price R.A., Stunkard A.J., Schulsinger F.: Geneticsof obesity in adult adoptees and their biological siblings. BMJ,1989; 298: 87-90
    Google Scholar
  • 101. Souza B.M., Assmann T.S., Kliemann L.M., Gross J.L., CananiL.H., Crispim D.: The role of uncoupling protein 2 (UCP2) on the developmentof type 2 diabetes mellitus and its chronic complications.Arq. Bras. Endocrinol. Metabol., 2011; 55: 239-248
    Google Scholar
  • 102. Ukropec J., Anunciado R.P., Ravussin Y., Hulver M.W., KozakL.P.: UCP1-independent thermogenesis in white adipose tissue ofcold-acclimated Ucp1-/ – mice. J. Biol. Chem., 2006; 281: 31894-31908
    Google Scholar
  • 103. Umekawa T., Yoshida T., Sakane N., Kogure A., Kondo M., HonjyoH.: Trp64Arg mutation of β3-adrenoceptor gene deteriorateslipolysis induced by β3-adrenoceptor agonist in human omentaladipocytes. Diabetes, 1999; 48: 117-120
    Google Scholar
  • 104. Urhammer S.A., Fridberg M., Sorensen T.I., Echwald S.M., AndersenT., Tybjaerg-Hansen A., Clausen J.O., Pedersen O.: Studies ofgenetic variability of the uncoupling protein 1 gene in Caucasiansubjects with juvenile-onset obesity. J. Clin. Endocrinol. Metab.,1997; 82: 4069-4074
    Google Scholar
  • 105. Urhammer S.A., Hansen T., Borch-Johnsen K., Pedersen O.:Studies of the synergistic effect of the Trp/Arg64 polymorphism ofthe β3-adrenergic receptor gene and the – 3826 A–>G variant of the uncoupling protein-1 gene on features of obesity and insulin resistancein a population-based sample of 379 young Danish subjects.J. Clin. Endocrinol. Metab., 2000; 85: 3151-3154
    Google Scholar
  • 106. van Marken Lichtenbelt W.D., Vanhommerig J.W., SmuldersN.M., Drossaerts J.M., Kemerink G.J., Bouvy N.D., Schrauwen P., TeuleG.J.: Cold-activated brown adipose tissue in healthy men. N. Engl. J.Med., 2009; 360: 1500-1508
    Google Scholar
  • 107. Vimaleswaran K.S., Radha V., Ghosh S., Majumder P.P., RaoM.R., Mohan V.: A haplotype at the UCP1 gene locus contributes togenetic risk for type 2 diabetes in Asian Indians (CURES-72). Metab.Syndr. Relat. Disord., 2010; 8: 63-68
    Google Scholar
  • 108. Vogler G.P., Sorensen T.I., Stunkard A.J., Srinivasan M.R., RaoD.C.: Influences of genes and shared family environment on adultbody mass index assessed in an adoption study by a comprehensivepath model. Int. J. Obes. Relat Metab Disord., 1995; 19: 40-45
    Google Scholar
  • 109. Walston J., Andersen R.E., Seibert M., Hilfiker H., Beamer B.,Blumenthal J., Poehlman E.T.: Arg64 β3-adrenoceptor variant andthe components of energy expenditure. Obes. Res., 2003; 11: 509-511
    Google Scholar
  • 110. Wijers S.L., Saris W.H., van Marken Lichtenbelt W.D.: Recentadvances in adaptive thermogenesis: potential implications for thetreatment of obesity. Obes. Rev., 2009; 10: 218-226
    Google Scholar
  • 111. Wójcik B.: Brunatna tkanka tłuszczowa u dorosłego człowieka:występowanie i funkcja. Endokrynologia, Otyłość i ZaburzeniaPrzemiany Materii, 2011; 7: 34-40
    Google Scholar
  • 112. Wu J., Bostrom P., Sparks L.M., Ye L., Choi J.H., Giang A.H.,Khandekar M., Virtanen K.A., Nuutila P., Schaart G., Huang K., TuH., van Marken Lichtenbelt W.D., Hoeks J., Enerback S. i wsp.: Beigeadipocytes are a distinct type of thermogenic fat cell in mouse andhuman. Cell, 2012; 150: 366-376
    Google Scholar
  • 113. Yoneshiro T., Aita S., Matsushita M., Okamatsu-Ogura Y., KameyaT., Kawai Y., Miyagawa M., Tsujisaki M., Saito M.: Age-relateddecrease in cold-activated brown adipose tissue and accumulationof body fat in healthy humans. Obesity, 2011; 19: 1755-1760
    Google Scholar
  • 114. Yoneshiro T., Ogawa T., Okamoto N., Matsushita M., Aita S.,Kameya T., Kawai Y., Iwanaga T., Saito M.: Impact of UCP1 and β3ARgene polymorphisms on age-related changes in brown adipose tissueand adiposity in humans. Int. J. Obes., 2013; 37: 993-998
    Google Scholar
  • 115. Yoshida T., Sakane N., Umekawa T., Sakai M., Takahashi T.,Kondo M.: Mutation of β3-adrenergic-receptor gene and responseto treatment of obesity. Lancet, 1995; 346: 1433-1434
    Google Scholar
  • 116. Yusuf S., Hawken S., Ounpuu S., Dans T., Avezum A., Lanas F.,McQueen M., Budaj A., Pais P., Varigos J., Lisheng L.: Effect of potentiallymodifiable risk factors associated with myocardial infarctionin 52 countries (the INTERHEART study): case-control study. Lancet,2004; 364: 937-952
    Google Scholar
  • 117. Zhang C., Rexrode K.M., van Dam R.M., Li T.Y., Hu F.B.: Abdominalobesity and the risk of all-cause, cardiovascular, and cancermortality: sixteen years of follow-up in US women. Circulation,2008; 117: 1658-1667
    Google Scholar

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