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Semin Plast Surg 2002; 16(2): 187-194
DOI: 10.1055/s-2002-32259
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Molecular and Genetic Mechanisms of Obesity

Molly S. Bray
  • Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX
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Publication History

Publication Date:
17 June 2002 (online)

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ABSTRACT

Obesity has been attributed to genetic, social, psychological, physiological, nutritional, and socioeconomic influences, indicating that multiple interacting variables likely affect body size and mass. In addition to environmental factors such as dietary intake and physical activity, research from both human and animal studies has provided substantial evidence for the contribution of genes in the determination of the obese phenotype. Nevertheless, identification of the genetic components influencing obesity is often difficult due to the multiplicity of contributing factors. This article briefly summarizes current strategies being used to elucidate genes and gene-environment interactions that play a role in the development of obesity. Because liposuction surgery is becoming increasingly utilized as an intervention for obesity, these strategies serve to illustrate the importance of considering the interaction between genes and environments when investigating the underlying etiology of obesity and response to treatment.

KEYWORDS

Obesity - liposuction - gene - obese phenotype

REFERENCES

  • 1 Hubert H B, Feinleib M, McNamara P M, Castelli W P. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study.  Circulation . 1983;  67 968-977
    CrossrefPubMedGoogle Scholar
  • 2 Feinleib M. Epidemiology of obesity in relation to health hazards.  Ann Intern Med . 1985;  103 1019-1024
    PubMedGoogle Scholar
  • 3 Garrison R J, Feinleib M, Castelli W P, McNamara P M. Cigarette smoking as a confounder of the relationship between relative weight and long-term mortality in the Framingham Study.  JAMA . 1983;  249 2199-2203
    CrossrefPubMedGoogle Scholar
  • 4 Lew E A, Garfinkel L. Variations in mortality by weight among 750,000 men and women.  J Chron Dis . 1979;  32 563-576
    CrossrefPubMedGoogle Scholar
  • 5 Rabkin S W, Mathewson F AL, Hsu P H. Relation of body weight to development of ischemic heart disease in a cohort of young North American men after a 26-year observation period: The Manitoba Study.  Am J Cardiol . 1977;  39 452-458
    PubMedGoogle Scholar
  • 6 Kral J G. Morbidity of severe obesity.  Surg Clin North Am . 2001;  81 1039-1061
    CrossrefPubMedGoogle Scholar
  • 7 NIH NIoH, NHLBI NHLaBI. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults Bethesda MD: National Institutes of Health National Heart Lung and Blood Institute; June 1998
  • 8 Kennedy G C. The role of depot fat in the hypothalamic control of food intake in the rat.  Proc Roy Soc Br Biol Sci . 1953;  140 578-592
    PubMedGoogle Scholar
  • 9 Hervey G R. The effects of lesions in the hypothalamus in parabiotic rats.  J Physiol . 1959;  145 336-352
    PubMedGoogle Scholar
  • 10 Harris R B. Role of set-point theory in regulation of body weight.  FASEB J . 1990;  4 3310-3318
    PubMedGoogle Scholar
  • 11 Flier J S. The adipocyte: storage depot or node on the energy information superhighway?.  Cell . 1995;  80 15-18
    CrossrefPubMedGoogle Scholar
  • 12 Zhang Y, Proenca R, Maffel M, Barone M, Leopold L, Friedman J. Positional cloning of the mouse obese gene and its human homologue.  Nature . 1994;  372 425-432
    CrossrefPubMedGoogle Scholar
  • 13 Considine R V, Sinha M K, Heiman M L. Serum immunoreactive-leptin concentrations in normal-weight and obese humans.  N Engl J Med . 1996;  334 292-295
    CrossrefPubMedGoogle Scholar
  • 14 Frederich R C, Hamann A, Anderson S, Lollmann B, Lowell B B, Flier J S. Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action.  Nat Med . 1995;  1 1311-1314
    CrossrefPubMedGoogle Scholar
  • 15 Halaas J L, Gajiwala K S, Maffei M. Weight-reducing effects of the plasma protein encoded by the obese gene.  Science . 1995;  269 543-546
    CrossrefPubMedGoogle Scholar
  • 16 Maffei M, Halaas J, Ravussin E. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.  Nat Med . 1995;  1 1155-1161
    CrossrefPubMedGoogle Scholar
  • 17 Pellymounter M A, Cullen M J, Baker M B. Effects of the obese gene product on body weight regulation in ob/ob mice.  Science . 1995;  269 540-543
    CrossrefPubMedGoogle Scholar
  • 18 Lonnqvist F, Arner P, Nordfors L, Schalling M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects.  Nat Med . 1995;  1 950-953
    CrossrefPubMedGoogle Scholar
  • 19 Hamilton B S, Paglia D, Kwan A YM, Dietel M. Increased obese mRNA expression in omental fat cells from massively obese humans.  Nat Med . 1995;  1 953-956
    CrossrefPubMedGoogle Scholar
  • 20 Cohen B, Novick D, Rubinstein M. Modulation of insulin activities by leptin.  Science . 1996;  274 1185-1188
    CrossrefPubMedGoogle Scholar
  • 21 Mueller G, Ertl J, Gerl M, Preibisch G. Leptin impairs metabolic actions of insulin in isolated rat adipocytes.  J Biol Chem . 1997;  272 10585-10593
    CrossrefPubMedGoogle Scholar
  • 22 Muoio D, Dohn G, Fiedorek F, Tapscott E, Coleman R. Leptin directly alters lipid partitioning in skeletal muscle.  Diabetes . 1997;  46 1360-1363
    PubMedGoogle Scholar
  • 23 Chen G, Koyama K, Yuan X. Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy.  Proc Natl Acad Sci USA . 1996;  93 14795-14799
    CrossrefPubMedGoogle Scholar
  • 24 Collins S, Kuhn C, Petro A, Swick A, Chrunyk B, Surwit R. Role of leptin in fat regulation.  Nature . 1996;  380 677
    CrossrefPubMedGoogle Scholar
  • 25 Lee G-H, Proenca R, Montez J M. Abnormal splicing of the leptin receptor in diabetic mice.  Nature . 1996;  379 632-635
    CrossrefPubMedGoogle Scholar
  • 26 Tartaglia L A, Dembski M, Weng X. Identification and expression cloning of a leptin receptor, OB-R.  Cell . 1995;  83 1263-1271
    CrossrefPubMedGoogle Scholar
  • 27 Takaya K, Ogawa Y, Hiraoka J, Hosoda K, Yamori Y, Nakao K. Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat.  Nature Genetics . 1996;  14 130-131
    CrossrefPubMedGoogle Scholar
  • 28 Chua Jr C S, Chung W K, Wu-Peng S. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor.  Science . 1996;  271 994-996
    PubMedGoogle Scholar
  • 29 Iida M, Murakami T, Ishida K, Mizuno A, Kuwajima M, Shima K. Substitution at codon 269 (glutamine to proline) of the leptin receptor (OB-R) cDNA is the only mutation found in the Zucker fatty (fa/fa) rat.  Biochem Biophys Res Commun . 1996;  224 597-604
    CrossrefPubMedGoogle Scholar
  • 30 Phillips M, Liu Q, Hammond H. Leptin receptor missense mutation in the fatty Zucker rat.  Nat Genet . 1996;  13 18-19
    CrossrefPubMedGoogle Scholar
  • 31 Wu-Peng X, Chua Jr S, Okada N, Liu S-M, Nicolson M, Leibel R. Phenotype of the obese Koletsky (f) rat due to tyr763stop mutation in the extracellular domain of the leptin receptor (Lepr).  Diabetes . 1997;  46 513-518
    PubMedGoogle Scholar
  • 32 Arner P. Obesity-a genetic disease of adipose tissue?.  Br J Nutr . 2000;  ppl 1 S9-S16
    PubMedGoogle Scholar
  • 33 Borecki I B, Rice T, Bouchard C, Rao D C. Commingling analysis of generalized body mass and composition measures: The Quebec Family Study.  Int J Obes . 1991;  15 763-773
    PubMedGoogle Scholar
  • 34 Rice T, Borecki I B, Bouchard C, Rao D C. Segregation analysis of fat mass and other body composition measures derived from underwater weighing.  Am J Hum Genet . 1993;  52 967-973
    PubMedGoogle Scholar
  • 35 Comuzzie A, Blangero J, Mahaney M. Major gene with sex-specific effects influences fat mass in Mexican Americans.  Genet Epidemiol . 1995;  12 475-488
    CrossrefPubMedGoogle Scholar
  • 36 Bouchard C, Rice T, Lemieux S, Despres J-P, Perusse L, Rao D. Major gene for abdominal visceral fat area in the Quebec Family Study.  Int J Obes . 1996;  20 420-427
    PubMedGoogle Scholar
  • 37 Moll P P, Burns T L, Lauers R M. The genetic and environmental sources of body mass index variability: The Muscatine Ponderosity Family Study.  Am J Hum Genet . 1991;  49 1243-1255
    PubMedGoogle Scholar
  • 38 Maes H, Neale M, Eaves L. Genetic and environmental factors in relative body weight and human adiposity.  Behav Genet . 1997;  27 325-351
    CrossrefPubMedGoogle Scholar
  • 39 Borjeson M. The aetiology of obesity in children: a study of 101 twin pairs.  Acta Paediatr Scand . 1976;  65 279-287
    PubMedGoogle Scholar
  • 40 Bodurtha J N, Mosteller M, Hewitt J K. Genetic analysis of anthropometric measures in 11-year-old twins: The Medical College of Virginia Twin Study.  Pediatr Res . 1990;  28 1-4
    PubMedGoogle Scholar
  • 41 Stunkard A J, Sorensen T IA, Hanis C. An adoption study of human obesity.  N Engl J Med . 1986;  314 193-199
    CrossrefPubMedGoogle Scholar
  • 42 Sorensen T, Stunkard C, Skovgaard L. Correlations of body mass index of adult adoptees and their biological and adoptive relatives.  Int J Obes . 1992;  16 227-236
    PubMedGoogle Scholar
  • 43 Echwald S, Sorensen T, Tybjaerg-Hansen A, Andersen T, Pedersen O. Gln27Glu variant of the human beta2-adrenoreceptor gene is not associated with early-onset obesity in Danish men.  Diabetes . 1998;  47 1657-1658
    PubMedGoogle Scholar
  • 44 Hellstrom L, Large V, Reynisdottir S, Wahrenberg H, Arner P. The different effects of a Gln27Glu beta 2-adrenoceptor gene polymorphism on obesity in males and in females.  J Intern Med . 1999;  245 253-259
    CrossrefPubMedGoogle Scholar
  • 45 Mori Y, Kim-Motoyama H, Ito Y. The Gln27Glu beta2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men.  Biochem Biophys Res Commun . 1999;  258 138-140
    CrossrefPubMedGoogle Scholar
  • 46 Meirhaeghe A, Helbecque N, Cottel D, Amouyel P. Beta2-adrenoceptor gene polymorphism, body weight, and physical activity.  Lancet . 1999;  353 896
    CrossrefPubMedGoogle Scholar
  • 47 Siffert W, Rosskopf D, Siffert G. Association of a human G-protein beta3 subunit variant with hypertension.  Nat Genet . 1998;  18 45-48
    CrossrefPubMedGoogle Scholar
  • 48 Schunkert H, Hense H, Doring A, Riegger G, Siffert W. Association between a polymorphism in the G protein beta3 subunit gene and lower renin and elevated diastolic blood pressure levels.  Hypertension . 1998;  32 510-513
    PubMedGoogle Scholar
  • 49 Benjafield A, Jeyasingam C, Nyholt D, Griffiths L, Morris B. G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension.  Hypertension . 1998;  32 1094-1097
    PubMedGoogle Scholar
  • 50 Siffert W, Naber C, Walla M, Ritz E. G protein beta3 subunit 825T allele and its potential association with obesity in hypertensive individuals.  J Hypertens . 1999;  17 1095-1098
    CrossrefPubMedGoogle Scholar
  • 51 Hegele R, Harris S, Hanley A, Cao H, Zinman B. G protein beta3 subunit gene variant and blood pressure variation in Canadian Oji-Cree.  Hypertension . 1998;  32 688-692
    PubMedGoogle Scholar
  • 52 Delva P, Pastori C, Provoli E. Erythrocyte Na(+)-H+ exchange activity in essential hypertensive and obese patients: role of excess body weight.  J Hypertens . 1993;  11 823-830
    CrossrefPubMedGoogle Scholar
  • 53 Hagberg J, Ferrell R, Katzel L, Dengel D, Sorkin J, Goldberg A. Apolipoprotein E genotype and exercise training-induced increases in plasma high-density lipoprotein (HDL)- and HDL2-cholesterol levels in overweight men.  Metabolism . 1999;  48 943-945
    CrossrefPubMedGoogle Scholar
  • 54 Hainer V, Stunkard A, Kunesova M, Parizkova J, Stich V, Allison D. A twin study of weight loss and metabolic efficiency.  Int J Obes Relat Metab Disord . 2001;  25 533-537
    CrossrefPubMedGoogle Scholar
  • 55 Sakane N, Yoshida T, Umekawa T, Kogure A, Kondo M. Beta2-adrenoceptor gene polymorphism and obesity.  Lancet . 1999;  353 1976
    PubMedGoogle Scholar
  • 56 Hunstad J. Body contouring in the obese patient.  Clin Plast Surg . 1996;  23 647-670
    PubMedGoogle Scholar
  • 57 Giese S Y, Bulan E J, Commons G W, Spear S L, Yanovski J A. Improvements in cardiovascular risk profile with large-volume liposuction: a pilot study.  Plast Reconstr Surg . 2001;  108 510-511
    PubMedGoogle Scholar
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